Stanford Synchrotron Radiation Lightsource

Olgotrelvir (STI-1558) is a novel antiviral drug designed to address the challenges posed by the emergence of new, more infectious and virulent SARS-CoV-2 variants. This drug is particularly important for populations at risk who may not benefit from existing treatments like Paxlovid due to potential drug-drug interactions. Olgotrelvir exhibits strong antiviral activity against the SARS-CoV-2 main protease (M^pro), including its variants which showed resistant to Paxlovid. Furthermore, it inhibits human cathepsin L (CTSL), a host enzyme critical for viral entry through the endosomal pathway, thereby blocking both the entry and replication of the virus. Phase 1 clinical trials have demonstrated that oral administration of Olgotrelvir achieves effective plasma levels with limited mild adverse effects and a promising reduction in viral RNA load.

Multiple sclerosis (MS) is a heterogeneous autoimmune disease in which autoreactive lymphocytes and antibodies attack the myelin sheath of the central nervous system (CNS). B lymphocytes in the cerebrospinal fluid (CSF) of MS patients contribute to inflammation and secrete oligoclonal immunoglobulins^1,2. Epstein-Barr virus (EBV) infection has been linked to MS epidemiologically, but its pathological role remains unclear^3,4.

Junctophilins (JPHs) are protein molecules that initiate junctions between the endoplasmic reticulum or sarcoplasmic reticulum and the plasma membrane of eukaryotic cells, enabling communication. Humans make four isoforms of JPH, which are expressed in different cell types. In heart muscle cells, isoform JPH2 is critical for converting electrical signals to a calcium ion signal that causes the cell to contract. 

Enzymes’ ability to speed biochemical reaction rates is the core of life processes, and much of molecular life science research involves understanding how an enzyme’s structure (often found through x-ray crystallography or NMR) is related to its function (biochemical analyses of the reaction). Pinpointing the 3D arrangement of atoms in the active site of an enzyme gives insight into the reaction intermediates and energetics, but may be conceptually misleading since enzymes, like all molecules, are constantly in motion

Nitrogen is an essential component for life and often a limiting factor for growth, despite the fact that air is composed of mostly nitrogen. The processing required to turn dinitrogen (N₂) gas into a form usable by most living organisms is rare in nature. Breaking the triple bond of N₂ requires the enzyme nitrogenase, which is found in some bacteria. The mechanism of nitrogenase, which uses metal ion containing cofactors to catalyze this energetically difficult reaction, is complex and difficult to decipher. A team of researchers has applied a new method to peek at the mechanism of the reaction by looking at the enzyme bound to its metal ion cofactors in an intermediate state.

The COVID-19 pandemic triggered by the SARS-CoV-2 coronavirus is causing health and economic havoc on a global scale requiring the development of an effective vaccine and therapeutics. Spike proteins found on the viral surface of SARS-CoV-2 attach to human cells to gain entry. Neutralizing antibodies which target these same spike proteins of the CoV-2 virus would effectively block viral entry.

A research team reviewed data on ~300 antibodies from convalescent patients that target SARS-CoV-2 and found that the gene IGHV3-53 was the most frequently used to produce these antibodies.

Organisms including microbes, plants, and animals can interpret light as a signal for action. While this is a fundamental and important process, the mechanism still holds mystery. How are photons converted into molecular signals? At the most basic step, a light-sensing molecule, a chromophore, undergoes a conformational change, an isomerization, when it encounters a photon. Many details are still unknown, which impacts efforts to engineer artificial light-sensing systems based on natural systems. A team of scientists has illuminated the importance of the immediate electrostatic environment of the chromophore on photoisomerization.

Implicated in human cancers including skin, prostate, colon, pancreatic, ovarian, endometrial, and lung, the protein called VISTA (V-domain Ig Suppressor of T-cell Activation) indirectly promotes cancer growth by interfering with T-cell function. In mouse models, antibodies against VISTA show anti-cancer activity, and are being developed by multiple pharmaceutical companies for evaluation in clinical trials.

Every year the flu vaccine contains a different formulation, due to multiple influenza virus strains and their ability to mutate. Scientists are working toward the universal flu vaccine, which would target conserved regions of the virus. Such a vaccine would be effective regardless of virus strain or genetic drift due to mutation, requiring no yearly updates. Current research focuses on the virus’s hemagglutinin (HA) stem region, which is targeted by our immune system’s broadly neutralizing antibodies (bnAbs). A team of researchers from Scripps and Janssen developed bnAbs to HA, which proved successful in preventing influenza infection in mice. Some of these are now being evaluated for effectiveness in human clinical trials. The team is now focused on finding an effective small molecule based on their bnAbs, which would have the advantage of oral delivery.

General anesthetics like alphaxalone (5α-pregnan-3α-ol-11,20 dione) bind to type A γ-aminobutyric acid receptors (GABA_ARs), which are gated ion channels that reduce the potential of neurons to fire. Experimental evidence points to GABA_AR’s transmembrane domain (TMD) as the allosteric site of drug binding. The TMD is known to be responsible for allowing the ion channel to transition between the resting, activated, and desensitized states. A team of scientists has studied where alphaxalone binds to GABA_AR and how this affects its function.

T cells allow our immune system to respond to specific antigens from infectious agents. Each T cell hosts a receptor (TCR) that binds to a particular antigenic peptide ligand. If the receptor is exposed to the ligand it recognizes, the T cell is activated. A team of researchers used a variety of methodologies including protein engineering, x-ray crystallography, single molecule techniques, and molecular simulations to understand how T cells recognize their ligands and subsequently how T cells are activated.

Imagine being born with severe muscle weakness. Several of your joints are contracted, your spine is abnormally curved, and you have an opening in the roof of your mouth, affecting your hearing, breathing and speech. On top of that, if you undergo surgery, you may die from a serious reaction to the anesthetics that causes your body temperature to rise to lethal levels.  This happens to people that have Native American Myopathy (NAM), a disorder first described for the Lumbee Native Americans in North Carolina, where about 1 in 5000 individuals is affected.

Cellular metabolism is essential for life. Up until recently, we knew just two methods cells use to generate and conserve the energy required for cellular metabolism: ATP hydrolysis and electrochemical ion potential across cell membranes. Recently, a paradigm-changing third mechanism was discovered, called flavin-based electron bifurcation (FBEB).

Iron-sulfur (Fe-S) clusters are cofactors that are required for the function of proteins in many critical cellular processes.  All living organisms synthesize and distribute Fe-S clusters using complex biosynthetic pathways. In humans, the mitochondrial cysteine desulfurase, NFS1, is responsible for the conversion of the sulfur-containing amino acid, cysteine, to alanine and persulfide sulfur, an intermediate in Fe-S cluster synthesis. In contrast to the analogous cysteine desulfurase in prokaryotes, the eukaryotic NFS1 enzyme requires accessory proteins, ISD11 and ACP, for its function. A team of scientists investigated the structure of the NFS1-ISD11-ACP complex in order to unravel NFS1’s requirement of ISD11 and ACP for function.

Using data collected at SSRL Beam Line 12-2, a team of scientists have determined the molecular structure formed between the Zika envelope protein and neutralizing human antibodies. 

The presence of the receptor tyrosine kinase Axl on tumor cells is correlated with disease severity and thus is an important oncology target. Developing inhibitors to Axl has been met with limited success due to the tight affinity with which Axl binds its ligand, growth arrest-specific 6 (Gas6). Researchers have engineered a soluble “receptor decoy,” called MYD1, based on Axl’s ligand-binding domain, that binds Gas6 even more tightly than Axl does.  

Many bacteria, including many colonizing our own gut biomes, produce hair-like pili structures on their surfaces. There are various types of pili used for different purposes, like exchanging genetic information (conjugation), movement, and adhesion. A bacterium builds pilus through oligomerization of protein subunits. A group of scientists have determined the structure of a new type of pilus, which they named the type V pilus.

Mutation of the gene coding for the BRAF kinase, an important enzyme in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, can lead to melanoma, an aggressive skin cancer. The pharmaceutical company Plexxikon has developed drugs, like vemurafenib, that treat metastatic melanoma harboring BRAF mutation.

While translocator proteins (TSPO) are clearly important for diverse organisms ranging from bacteria to humans, their roles in cells are not yet fully understood. TSPO is positioned in the outer mitochondrial membrane and binds small molecules, such as benzodiazepine, cholesterol, and porphyrin molecules. It has been implicated as having a role in a number of human diseases, including Parkinson’s and Alzheimer’s, as well as inflammation and tumor growth.

Scientists have developed a goniometer-based system to study radiation-sensitive macromolecular complexes.

Creating novel enzymes to perform specific chemical reactions is a field of great promise, but it is still in its early stages. Efforts usually involve using well-studied protein structural and functional domains to create new active sites. Scientists have recently developed a different approach, creating the active site in the interface between proteins in a multi-protein complex. They started with a well-researched, natural protein that, in its natural state, does not form complexes with other proteins, and nor does it catalyze the desired reaction.

With more viruses that infect bacteria than any other type of biological entity, bacteria have developed a sophisticated means of defending themselves. At the heart of their defenses is a system called CRISPR.

Influenza viruses infect millions of people each year, cause severe illness, and present a significant health challenge. Vaccines are effective in preventing the flu but they require almost yearly reformulation to keep up with the constantly changing viruses. The highly variable hemagglutinin (HA), the major surface glycoprotein on influenza viruses, binds host cells to initiate infection. Scientists have identified a broadly neutralizing antibody, F045-092, that can inhibit this binding.

As a crucial part of an organism’s immune system, T cells detect and fight infection and cellular dysfunction. Each T cell has a unique T-cell receptor (TCR) on its surface that recognizes and binds peptide antigens, triggering an immune response. The peptide antigens themselves, often stemming from intruding organisms such as bacteria, are bound to molecules known as major histocompatibility complexes, or MHCs. TCRs show a great deal of diversity in order to ensure that the large number of potential antigens can be detected. Although of great medical interest, predicting what peptides a given TCR recognizes has been challenging. A team led by researchers has now found a way to increase the success of such predictions from 30 to up to 90 percent.

Fatty acids are key components of a variety of biological functions ranging from cellular membranes to energy storage. In addition, they are of great interest as potential “green” biofuels and targets in the development of novel antibiotics. In order to fully exploit their potential, researchers must first understand in detail how organisms synthesize fatty acids. However, due to the dynamic nature of the process, structural and functional studies of fatty acid biosynthesis are very challenging. A team of scientists has recently made a giant leap forward by determining the structure of a protein–protein complex that represents a snapshot of fatty acid biosynthesis in action.

During evolution, organisms added new domains to tRNA synthetases, which are believed to enable additional functions beyond protein synthesis. For the very first time researchers have established an essential role for an appended domain of tRNA synthetase in organisms.

Cells bind each other using specialized cell surface adhesion complexes called adherens junctions. These complexes direct the formation of tight, Velcro-like contacts that are essential for the development, architecture, maintenance, and function of tissues in all higher organisms. Exactly how this cell to cell binding is accomplished has not been fully understood.  Researchers from the Florida campus of The Scripps Research Institute (TSRI) have now solved a piece of this puzzle by determining the structure of α-catenin using SSRL’s Beam Line 11-1.

Cys-loop receptors in eukaryotic cells control fast synaptic transmission and are important targets for various therapeutics which include general anesthetics. Although technical challenges have limited the determination of high-resolution structures for Cys-loop receptors, researchers from the University of Pittsburgh School of Medicine have taken advantage of two homologous proteins: the pentameric ligand-gated ion channels (pLGICs) found in the bacterium Erwinia chrysanthemi (ELIC) and the cyanobacterium Gloebacter violaceus (GLIC). The researchers carried out crystallographic studies of these pLGICs on SSRL Beam Line 12-2, investigating the structural underpinnings of the pLGIC activation process and the structural basis of anesthetic modulation of pLGICs.

Botulinum neurotoxins (BoNTs) invade motor neurons at their junctions with muscular tissue, where the toxins disable the release of the neurotransmitter acetylcholine and subsequently paralyze the affected muscles. Accidental BoNT poisoning primarily occurs through ingestion of food products contaminated by Clostridium botulinum, the bacterium that produces BoNTs. However, BoNTs by themselves are fragile and sensitive to low pH environments and digestive proteases. So how do they survive the harsh environment of the host’s gastrointestinal tract?

Flavin-dependant thymidylate synthases (FDTSs) are a class of recently identified family of thymidylate synthases that employ novel mechanism for the thymidylate synthase reaction.   Thymidylate synthases use N⁵,N¹⁰-methylene-5,6,7,8-tetrahydrofolate (CH₂H₄folate) to reductively methylate 2’-deoxyuridine-5’-monophosphate (dUMP) producing 2’-deoxythymine-5’-monophosphate (dTMP).  dTMP is one of the four DNA building blocks and is crucial for survival of all organisms.  Unlike other deoxynucleotides, dTMP cannot be directly synthesized by a ribonucleotide reductase, and its de novo biosynthesis requires the enzyme thymidylate synthase. Therefore, inhibition of thymidylate synthesis stops DNA production, arresting cell cycle and eventually leading to “thymineless” cell death.  The human enzyme has long been recognized as a target for anticancer drugs.

Since FDTS enzymes are mainly found in very pathogenic microbes including the pathogens causing leprosy, botulism, diarrhea, anthrax, pneumonia, syphilis, etc., the FDTS enzyme is an attractive target for antibiotic drugs.

Botulinum neurotoxin is produced by the bacteria Clostridium botulinum and is the most potent toxin known, inducing a potentially fatal paralysis known as "botulism." Botulism can occur in a number of ways, including infection through open wounds or in the intestinal tract, or after consuming contaminated food in which toxin has been produced. In the USA, infant botulism is the most common manifestation of the disease-some speculate whether its prevalence is linked to sudden infant death syndrome. On the other hand, these neurotoxins have also become a powerful therapeutic tool for treating a variety of neurological, ophthalmic, and other disorders manifested by abnormal, excessive, or inappropriate muscle contractions.

Botulinum neurotoxin is produced by the bacteria Clostridium botulinum and is the most potent toxin known, inducing a potentially fatal paralysis known as "botulism." Botulism can occur in a number of ways, including infection through open wounds or in the intestinal tract, or after consuming contaminated food in which toxin has been produced. In the USA, infant botulism is the most common manifestation of the disease-some speculate whether its prevalence is linked to sudden infant death syndrome. On the other hand, these neurotoxins have also become a powerful therapeutic tool for treating a variety of neurological, ophthalmic, and other disorders manifested by abnormal, excessive, or inappropriate muscle contractions.

Researchers from the University of California, Santa Cruz, using macromolecular crystallography Beam Line 9-1 at SSRL have determined the three-dimensional structure of an RNA enzyme, or "ribozyme," that carries out a fundamental reaction required to make new RNA molecules. Their results provide insight into what may have been the first self-replicating molecule to arise billions of years ago on the evolutionary path toward the emergence of life. The findings are published in the March 16 issue of the journal Science.

Adaptive immunity relies on the capacity of immune cells to distinguish between the body's own cells and foreign invaders. T-cells are the foot soldiers of the immune system, and they carry receptors that undergo an extensive "education" process for recognizing specific proteins from these invaders. Mature T-cells also show the ability to recognize proteins for which they have not been exposed to. How the T-cell receptors (TCRs) achieve this ability is poorly understood. It is this same immune response which causes T-cell mediated rejection in organ transplant patients, and solving this problem could lead to new ways of combating tissue rejection.

Severe acute respiratory syndrome (SARS) emerged as the first severe and readily transmissible new disease of the 21st century. The debilitating pneumonia-like disease is caused by coronavirus, which caused 916 deaths out of about 8,400 reported cases. Scientists from The Scripps Research Institute in California have embarked on an ambitious program to characterize the structure and function of all the proteins built or used by SARS. Taking advantage of advances in robotics and automation at Stanford Synchrotron Radiation Laboratory as well as other new tools, the scientists ultimately hope to rapidly characterize the complete protein sets of emerging disease organisms and then provide structure information to design inhibitors to stop the organisms.

X-ray crystallography studies at the Stanford Synchrotron Radiation Laboratory recently shone light on a human enzyme that helps synthesize heme, the iron-containing pigment that helps carry oxygen to all parts of our bodies. There are many enzymes along the chemical pathway that produces heme. Defects in any one of the enzymes cause different types of porphyria, a set of symptoms that includes acute pain, neurological problems, and even the madness suffered by King George III.

After years of wondering how organisms managed to create medically valuable natural products, like antibiotics and anti-fungal agents, chemists have discovered the surprisingly simple secret by shining x-ray light on the problem. MIT and Harvard researchers used crystallography beam lines at the Stanford Synchrotron Radiation Laboratory and the Advanced Light Source in Berkeley for their research.

Researchers have for the first time obtained a high-resolution structure of a three-molecule receptor-ligand complex that could help shed light on neurodegenerative diseases such as Parkinson's. The complex includes two receptor molecules, called GFRα3, bound with its ligand, artemin, which fit together like a lock and key. These molecules play a key role in chemical signal transmission and in the development and health of neurons.

Life as we know it depends on turning on and off the proper genes at the correct time. This process of gene expression starts when an RNA message is copied from DNA. Scientists have long known that an enzyme called RNA polymerase II plays the central role in this delicate transcription process. But the exact mechanism by which RNA polymerase II selects specific nucleotides and catalyzes the reaction that incorporates them into a growing RNA strand has not been well understood.

We have to defend ourselves from the challenge of microbial pathogens every day. Innate immune system represents the first line of defense against microorganisms by selectively detecting foreign molecules. The Toll-like receptors (TLRs) are one of the most important sensors of the innate immune system and recognize conserved molecules from various pathogens including viruses, bacteria, fungi and parasites.

Ion channels in our cells generate the nerve impulses that enable the heart to beat, the body to move, and sensation and thought to occur. Scientists from the Salk Institute for Biological Studies have identified a tiny flexible gateway that controls the rapid-fire opening and closing of a family of ion channels through which nerve-triggering potassium ions flow in and out of cells of the body. Malfunctions in the channels leads to several human diseases, including epilepsy, cardiac arrhythmias and muscle disorders.

The Botox^® face lifts and botulism disease are both caused by a neurotoxin from the bacterium Clostridium botulinum. The toxin, often described as the most lethal substance known, is a member of the clostridal neurotoxins (CNTs) group, which block muscle contractions. When injected into someone's face, the effect is a lessening of wrinkles. When ingested, the toxin paralyzes muscles, including those of the internal organs, causing sickness and death. The toxin is also used in medicine for conditions such as uncontrolled blinking, lazy eye, and involuntary muscle contractions.

Error-free DNA replication depends on the maintenance of the correct chemical structure of each component base. Bases with altered structures may mispair during the replication process, causing mutations. One common chemical alteration is the addition of an alkyl group to guanine, causing mispairing to thiamine during replication.

Researchers have literally unearthed clues as to why the 1918 influenza pandemic was so deadly. The 1918 influenza pandemic ranks as the largest and most destructive outbreak of an infectious disease, killing 20 to 40 million people worldwide. Using fragments of the flu genome from Alaskan victims preserved by permafrost and army autopsy tissues, James Stevens and Ian Wilson of the Scripps Research Institute in La Jolla, California and their collaborators have assembled genes from the 1918 flu virus.

Prostate cancer, the most common cancer in men, is often a localized, slow-growing cancer, which aids treatment and improves survival rates.  However, highly aggressive, metastatic forms of the cancer occur frequently enough to make it the No. 2 cause of death in U.S. men.  Part of the reason for this high mortality rate is the lack of effective drugs to fight these more aggressive cancers. 

When a blood vessel is cut, the body activates a repair mechanism that eventually seals the cut and prevents further blood loss. This life saving process becomes life threatening when clots form inside a functional blood vessel. Arrest of bleeding works through platelet adhesion and thrombin-induced fibrin formation at the site of injury. In order for the platelets to stick to the injured tissues and to each other, they need to be activated. Thrombin is an essential protease (a type of enzyme) that activates platelets and forms blood clots in response to vascular injury.

The rise in obesity in the United States parallels a dramatic increase in obesity-associated diseases, most notably type-2 diabetes. This disease is predicted to reach epidemic proportions in the next several decades (Zimmet et al 2001, Urek et al 2007). Thus, understanding the biochemical processes underlying type-2 diabetes and identifying new targets for therapeutic intervention are critical for national and world health.

One of the primary ways people find structure and coherence in the world is to identify fundamental characteristics common within and between apparently different classes - plants, humans, atoms, stars, etc. In the case of diverse biological life we know that RNA and/or DNA are common to them all. Thus, a deeper understanding of the architecture and interactions of RNA and DNA will lead to a greater understanding of the commonalities underlying all biological life.

Autism is a neurodevelopmental disorder that impairs social interactions, and causes communication deficits and repetitive behaviors. About 1 in every 150 children is affected by autism. Genetic screens revealed that mutations in the neurexin and neuroligin genes are among the multiple genetic causes of autism spectrum disorders and mental retardation (Jamain et al., 2003; Szatmari et al., 2007).

Proteins are transported to specific sites within cells enclosed in packets called transport vesicles, along a specialized network of tracks called microtubules. Transport vesicles are targeted to the correct acceptor membrane by a number of sequential steps that are regulated by small GTPases of the Rab and Arf families. The initial interaction between vesicles and the target membrane is thought to be mediated by very large molecular "tethers" that link the two membranes prior to fusion. A Stanford team from the Brunger and Pfeffer laboratories has studied how one such putative tether molecule is localized to the membranes of an organelle called the Golgi complex.

TGF-beta is the founding member of a large family of biological molecules important in regulating cellular growth and differentiation, both in embryos as well as adults. Now, using x-ray diffraction at SSRL Beam Line 11-1 for macromolecular crystallography, Groppe, Hinck, and colleagues from the University of Texas Health Science Center at San Antonio have determined the structure of TGF-beta in complex with two of its cellular receptors, a finding that could lead to new insight as to how it functions as a suppressor of cell growth and as a stimulator of cell differentiation, processes which go awry in diseases such as cancer. The results are published in the February 1 edition of Molecular Cell.

Scientists are one step closer to understanding a piece of the machinery involved in DNA transcription and repair, thanks to work done in part at the SSRL macromolecular crystallography Beam Line 11-1. The team, led by The Scripps Research Institute researcher John Tainer, and colleagues worked out the structure of an important enzyme call XPD, a member of the helicase family of enzymes, found in all living organisms. The results were published in the May 2008 edition of the journal Cell.

Scientists have recently identified a family of human antibodies that can take out an unprecedented number of different types of flu viruses, including H5N1 'bird flu' and the 1918 H1N1 'Spanish flu', which killed millions around the world during World War I, as well as seasonal flu. Using SSRL's Beam Line 9-2, Dr. Robert Liddington from the Burnham Institute for Medical Research led a team of scientists that determined the crystal structure of one such antibody, F10, in complex with the hemagglutinin H5 to unveil the molecular mechanism of virus neutralization. Results were published online 22 February 2009 in the journal Nature Structural and Molecular Biology.

Medications can be rendered ineffective through cells developing multidrug resistance. This is the case in many forms of cancer cells that fail to respond to chemotherapy. The ability of these cells to avoid the effects of drugs can be due to the actions of P-glycoprotein (P-gp). This protein sits in the membranes of cells and acts like a pump. It ushers a wide range of potentially harmful molecules from inside the membrane to outside the cell. Unfortunately, it can also mediate the removal of life-saving medications.

DNA is a relatively stable molecule, but it can be damaged by chemicals generated inside our cells or by radiation originating from outside our cells. Significant amounts of DNA damage can lead to rapid-aging, cancer, and other diseases, so the cell has a fleet of enzymes that specialize in combating this daily wear-and-tear. One important group of DNA repair enzymes is the Rad60 family of proteins that is highly conserved from yeast to humans.

UC Irvine researchers have unveiled the mystery behind one of the deadliest toxins that causes liver cancer. Aflatoxins are common contaminants of foods such as nuts and grains, which make up the staple diets of many developing countries. These toxins are produced by moldy fungi during food production, and are considered by the FDA to be an unavoidable food contaminant. Aflatoxin molecules are characterized by the presence of multiple aromatic rings. Chronic ingestion of aflatoxin B1 leads to liver tumors that are a major cause of death in Asia, Africa, and Central America. This toxin wreaks havoc of p53, an important gene in our body that prevents cancer. Without the protective effect of p53, then, aflatoxin further compromises immunity, interferes with our body metabolism, and causes severe malnutrition. It is urgently important to find inexpensive strategies that help protect the world population from aflatoxin food contamination.

In order for our eyes to see in both intense and low light conditions, molecular mechanisms allow for light and dark adaptation. The G-protein transducin is responsible for transducing signal from the photon receptor protein rhodopsin in rod and cone photoreceptors of our retina. Transducin is composed of three polypeptides, α, β and γ. The α subunit contains the GTP binding site. While waiting for a signal from rhodopsin, transducin is bound to the outer segment of the neuron. During exposure to normal daylight, transducin becomes displaced and migrates to another part of the cell: the photoreceptor is adapting to light. In darkness or very dim light, transducin will return to its “home” membrane. 

Cytokines are central to the innate immune system. Type I interferons (IFNs) are a kind of cytokine signaling protein that is important for cellular communication, regulating diverse cellular processes.  Showing surprising economy, just one receptor is responsible for binding a variety of IFNs, each with differing functions.

Diatoms, unicellular algae that exist almost anywhere there is water, have recently attracted attention as potential thwarters of climate change. Diatoms go through cycles of blooms, where they grow and multiply rapidly near the ocean's surface. Scarcity of a nutrient will trigger the end of a bloom and the algae sink, taking with them large amounts of sequestered carbon from the air to the bottom of the ocean. Because iron is a limiting nutrient in about 30-40% of the world's oceans, some researchers propose that artificially enriching iron in oceans would promote diatom growth and carbon dioxide capture similar to the hypothesized scenario that occurs during glacial periods when iron input into the ocean is higher.

The smallest organisms should not be overlooked when finding solutions to the problem of increasing pollutants and greenhouse gases in our atmosphere. Each year, some microorganisms using the enzyme carbon monoxide dehydrogenase (CODH) take an estimated 100 million tons of carbon monoxide (CO) from our air, while others use CODH to produce 10 billion tons of acetate from carbon dioxide (CO₂).

MATE transporters are responsible for the exportation of various substrates and toxins from cells of bacteria, plants, and mammals using a proton or sodium gradient. Plants use them to transport metabolites, and they are important for tolerance to aluminum in soil, an important factor for crop yield. In bacteria and mammals, MATE transporters are important for multiple-drug resistance, which affects the efficacy of many medicines. Although these transporters play such important roles, much about how they work is not understood.

Cisplatin, a platinum-based anti-cancer drug, is a widely-used and effective cancer chemotherapy drug. It slows the growth of cancer cells by inhibiting transcription through DNA modification, creating chemical links that serve as a roadblock as the polymerase attempts to transcribe the DNA into RNA.

Messenger RNA, responsible for relaying information from the DNA to the ribosomes, is given a 5’ cap and a 3’ tail. The 3′-end cleavage and polyadenylation are performed by a large protein complex that includes a scaffolding protein called symplekin.

At times, different observational tools do not give the same answer when measuring the same thing.  Such was the case when looking at the metalloenzyme transition state species Fe(IV)-O, important as an oxidant in a number of iron-containing enzymes. While x-ray absorption spectroscopic experiments determined the Fe-O bond length to be short (less than 1.7 Å), some results from crystallographic studies indicated that the bond length was longer (1.8-1.9 Å).

The selection and transcription of specific areas of DNA is a critical part of gene expression. Genes that code for proteins are transcribed into messenger RNAs by RNA polymerase II. This enzyme is recruited to parts of the genome by a number of transcription factors, which bind to particular DNA sequences like the TATA box. The transcription factor TFIIB brings the polymerase and the proper DNA sequences close together, and it helps define the direction of transcription.

For decades, people have been using penicillium mold and molecules produced by soil bacteria as a means of fighting off harmful bacteria and treat infection. But resistance to these chemicals is now becoming commonplace. Today many infections are resistant to not only penicillin but also other β-lactam antibiotics, some of which are classified as “last line of defense” drugs for E. coli and Klebsiella pneumoniae.

Biological macromolecules, like proteins and nucleic acids, are good examples of the form follows function paradigm; and, in the case of these molecules, deformation follows function as well. Flexibility in proteins and nucleic acids allows for the recognition of targets, the binding of complexes, and the adoption of functional configurations. Recent research at SSRL Beam Line 12-2 has revealed how distortion in macromolecular structure is linked to function. BL12-2 is the high-intensity, state-of-the-art undulator beam line for advanced macromolecular crystallographic studies funded by The Gordon and Betty Moore Foundation in cooperation with the California Institute of Technology.

Prions are self-propagating protein aggregates that are the infectious element of fatal neurodegenerative disease in mammals. In fungi, however, prions act as protein-based genetic elements. The fungal prion proteins have a so-called prion-forming domain (PFD) that is natively unfolded in its soluble form attached to a globular domain that can regulate the prion in cis. Upon interaction with the prion, an amyloid cross-baggregate form of the protein, the PFD, undergoes a structural rearrangement into an identical amyloid state.

The structure of human FEN1 as it interacts with a strand of DNA has now been solved by an international team of scientists led by Lawrence Berkeley National Laboratory and the Scripps Research Institute in La Jolla, conducting their work at both the Stanford Synchrotron Radiation Lightsource and the Advanced Light Source. Previous work determined FEN1's structure when not acting on DNA; but how the protein works was not apparent in this DNA-free structure. The recent work, published in the April 15 edition of Cell, reveals how FEN1 goes about its task of removing excess single-strand DNA during DNA replication.

The enzyme nitrogenase plays a critical role in converting nitrogen in the air into ammonia, a form that living organisms can use. Scientists have long sought to understand where at the active site of this enzyme, and how, this reaction takes place; among other things, they hope to eventually reverse-engineer it and replace the resource-intensive method widely used in industry with one that mimics nature's gentle version of the reaction.

The ability of organisms to sense and respond to light availability is of great interest to those wishing to exploit these mechanisms in the areas of biotechnology and agriculture. A particular light sensing domain, termed the light-oxygen-voltage (LOV) domain, is found in plants, animals, and bacteria to control a wide variety of biological processes^1-5. LOV domains oftentimes signal to a variety of attached effector domains including kinases, F-boxes, and DNA-binding domains.

Strategies to combat HIV require structural knowledge of how antibodies recognize HIV envelope proteins and how they are used by the immune system to eliminate viruses and virally-infected cells. A few years after infection, some HIV-infected patients develop broadly neutralizing antibodies (bNAbs), which neutralize across many HIV strains and confer protection against simian immunodeficiency virus (SIV) infection in non-human primates when delivered by passive immunization (i.e. purified Abs were injected).

Transport proteins, embedded in lipid membranes, facilitate the import of nutrients into cells or the release of toxic products into the surrounding medium. The largest and arguably the most important family of membrane transport proteins are the ABC transporters. They are ubiquitous in biology and power the translocation of substrates across the membrane, often against a concentration gradient, by hydrolyzing ATP (Higgins, 1992).