Previous Editions

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SSRL Headlines Vol. 8, No. 7  January, 2008

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Contents of this Issue:

  1. Science Highlight — A New Window on a Well-Known Family of Proteins
  2. Science Highlight — GTPase Family Proteins Show Microscopic Teamwork
  3. Budget May Impact User Operations
  4. Unique SSRL-Stanford Collaboration Illuminates Rare Materials
  5. SSRL Users' Organization Update
  6. Princess Sumaya of Jordan Visits SLAC
  7. Upcoming Beam Time Request and Proposal Deadlines
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1.  Science Highlight — A New Window on a Well-Known Family of Proteins
       (contacts: D.E. Dollins, J.J. Warren, R.M. Immormino and D.T. Gewirth, HWI)

Overview of the GRP94 structure.
Researchers from the Hauptman Woodward Medical Research Institute, working in part at SSRL's Beam Line 11-1, have used x-ray diffraction data to confirm a family linkage between the mammalian protein GRP94 and the better known HSP90 proteins, whose functions range from signal transduction to immune response. It is the first high resolution picture of any member of the HSP90 family. Therapies that target GRP94, an essential endoplasmic chaperone (chaperones assist the newly synthesized proteins to achieve their final fold), might play a role in the treatment of immune diseases like sepsis, heart disease, and cancer. The results were published in the October 2007 issue of Molecular Cell.

The structural study and further experiments showed for the first time that GRP94 has a very weak but reproducible ATPase activity. The studies also suggested that the transition from the "twisted V" conformation to one that aligns the catalytic residues was likely to be a key step in the regulation of GRP94 activity. The mammalian member of this HSP90 family is different than those previously studied, which were derived from either bacteria or yeast. The cytoplasmic human Hsp90 exhibits unusually weak ATPase activity, and thus may bear a strong structural resemblance to GRP94. This means that the insights gained by a greater scientific understanding of how GRP94 works will have more direct application to human diseases.

Crystal screening and data collection were carried out using SSRL's user remote-access system, enabling the research group to perform (and control) the experiment from their home laboratory.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/grp94-nucleotide.html


2.  Science Highlight — GTPase Family Proteins Show Microscopic Teamwork
       (contacts: A. Schweizer Burguete, T.D. Fenn, A.T. Brunger and S.R. Pfeffer, Stanford University)

Model for dual GTPase binding to adjacent RBD and GRIP domains in GCC185.
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. The work shows that binding of the tethering protein to the Golgi requires cooperation between two families of GTPases: the Rab family and the Arl family. Only together could the two membrane-attached GTPases provide stable binding of the tether to the Golgi complex.

Using x-ray diffraction data collected at SSRL, researchers Alondra Schweizer Burguete and Timothy Fenn determined the structure of a region of the tether in complex with the Rab6 GTPase. They created a model of the system to visualize how the GTPases might cooperate to anchor the tether and thereby capture incoming vesicles. In this model, proteins belonging to the Rab and Arf GTPase families reside at the membrane-anchor point of the tether. A pair of Arl1 GTPase molecules form a previously characterized complex with the tether close to the membrane. At a significant distance (10 nanometers) away from the membrane, a pair of Rab6 molecules bind a distinct tether-region; the Rab GTPases are able to reach this far thanks to their extended and unstructured tail-domains.

The model explains how Arl1 and Rab6 GTPases may cooperate in anchoring the tether to the Golgi membrane, thereby directing incoming vesicles to the Golgi membrane prior to fusion. This represents a first-ever instance of such a cooperative relationship among different members of these GTPase families.

The results are published in the January 25 edition of the journal Cell.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/rab-arl_gtpases.html

see also: SLAC TODAY article at: http://today.slac.stanford.edu/feature/2008/cell.asp


3.   Budget May Impact User Operations
       (contact: C. Knotts, knotts@slac.stanford.edu)

As you may already know, the FY08 budget for science was much less than expected. This will likely result in reduced operational hours at many DOE funded facilities, including SSRL. We are currently assessing the situation and discussing the potential impact on user operations with the SSRL Users' Organization Executive Committee.

4.   Unique SSRL-Stanford Collaboration Illuminates Rare Materials
      —SLAC Today article by Heather Rock Woods

Rob Moore at Beam Line 5-4
Take two high-tech x-ray beam lines, a table-top apparatus, half a dozen researchers and a material made with one of the rarest elements on earth. Combine them in a collaborative venture to bring to light the best, first clear picture of the material's properties. That is the heart of recent work done at the Geballe Laboratory for Advanced Materials at Stanford University and at Beam Lines 5-4 and 7-2 at the Stanford Synchrotron Radiation Laboratory (SSRL). Such a synergistic effort is an example of how to solve one puzzle by applying the power of multiple researchers and approaches. Combining their resources and techniques, the researchers examined little-studied compounds made of tellurium-a semi- metal that is one of the rarest elements on earth-and one of the "rare earth" elements, which actually aren't so rare.

With three different techniques brought to bear on these rare-earth tri-telluride compounds, "We get a much more complete picture," said SSRL physicist Mike Toney. "All of the studies are complementary, related to understanding the same phenomenon."

The phenomenon is the formation of a "charge density wave," a kind of electronic instability where the electrons aren't where you'd expect them to be inside the material. The movement of electrons to those new locations also distorts the positions of atoms within the material, changing aspects of the material's behavior.

At the Geballe Lab, Nancy Ru and Ian Fisher used their table-top lab equipment to run current through the materials to measure the resistance to electron flow at different temperatures. These data provided the first evidence for the occurrence of electronic instabilities in these materials, and indicated the most interesting temperature regions for the two groups at SSRL to investigate. At BL5-4, Rob Moore and Z.-X. Shen of SLAC's X-ray Laboratory for Advanced Materials (XLAM) shone intense UV-light on the material to eject electrons and then analyze their energy and momentum using a technique called Angle-Resolved Photoemission Spectroscopy (ARPES). This technique reveals the material's electronic structure-where the electrons are-and how it changes due to the existence of the charge density wave. On BL7-2, Ru, coworker Kyungyun Shin, SSRL postdoctoral researcher Cathie Condron, Fisher and Toney sent x-rays through the material to get diffraction patterns at different temperatures. These patterns showed changes in the atomic structure that were directly correlated with changes in the electronic structure observed in the ARPES data. The combined results enable a deeper understanding of the driving forces behind the changes in atomic and electronic structure in this and related materials.

"Understanding a simpler system like this might help us understand why materials behave this way," said Moore. "The ultimate goal is to understand the fundamental physics so we could design materials with properties we desire, such as superconductors that operate at room temperature."


5.   SSRL Users' Organization Update
       (contact: R. Szilagyi, szilagyi@montana.edu, SSRLUOEC Chair)

The SSRL Users' Organization Executive Committee (SSRLUOEC) met recently on December 14 and January 31. Several topics were discussed at these meetings, including the draft SSRLUOEC charter (review at http://www-ssrl.slac.stanford.edu/users/ssrluo/ssrluo_charter.html), plans for the 2008 user survey, plans for the 2008 SSRL/LCLS Users' Meeting, and User Outreach/Activism. The SSRLUOEC is also meeting with SSRL management to discuss the impact of the reduced budget on user operations as well as future plans for SSRL. All users are invited to participate in these meetings, and notes from the meetings are posted on the web to keep users informed about committee activities, see http://www-ssrl.slac.stanford.edu/users/ssrluo/minutes_dec07.html.

Even if you are unable to attend the users' organization meetings, we encourage you to share your feedback and suggestions with us by contacting anyone on the committee http://www-ssrl.slac.stanford.edu/users/ssrluo/ssrluoec-fy08.html, or by completing the on-line user survey which we are now conducting at https://www.surveymonkey.com/s.aspx?sm=o5ICDralcEn8kpFsqSgKEA_3d_3d This survey is a follow up to the one conducted last year, and something which we plan to do annually. The user survey serves as a very important communication channel between the SSRL user community and the SSRL Users' Organization Executive Committee. We will use your feedback via this survey to organize the next SSRL/LCLS Users meeting, to prepare reports to SSRL management as well as advisory and review committees, and of course to continue to improve the overall user experience at SSRL both in science and otherwise. The survey has only 10 questions, is designed to be straightforward, and is estimated to only take ~15 minutes to complete. Wherever you see a box for comments, we invite you to elaborate beyond just the specific survey questions. As an added incentive, we will have a random drawing of several prizes including a free night stay at the Guest House, SSRL shirts, SSRL baseball caps, and SSRL coffee mugs for users who complete the survey.

We thank you in advance for your input on the survey and for participating in user advocacy activities such as the email writing campaign to positively affect the future of science in the US (Response by SSRL users was among the highest - way to go SSRL users!). Best wishes for a successful 2008!


6.   Princess Sumaya of Jordan Visits SLAC
      —SLAC Today article by Kelen Tuttle

Herman Winick showing Princess Sumaya bint El Hassan of Jordan a piece of SSRL history—the first wiggler which was installed on BL4 in 1978.
Her Royal Highness Princess Sumaya bint El Hassan of Jordan visited SLAC last Friday for a tour of the lab and meetings with researchers. The Princess plays a major role in education, science, and technology in Jordan. For example she is the head of the Princess Sumaya University for Technology (PSUT) Board of Trustees and the President of the Royal Scientific Society (RSS).

She came to SLAC primarily to see SSRL in operation as a model for SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East), a UNESCO sponsored project in construction in Jordan as a collaboration among 10 Middle East countries.

After meeting with Persis Drell and other directorate members, Princess Sumaya toured the laboratory with Keith Hodgson and host Herman Winick, who, along with Gus Voss of DESY, initiated the SESAME Project in 1997. Uwe Bergmann explained how x-rays can be used to read overwritten ancient manuscripts, and Les Cottrell talked about the digital divide with emphasis on the Middle East. After visiting SLAC she had lunch with President Hennessy and Arthur Bienenstock. Following this she gave a talk and had spirited exchanges with Stanford faculty and students at the Center for Democracy, Development and the Rule of Law on the Stanford campus.

"In her interactions she proved to be charming, as well as articulate about the problems in Jordan and the Arab world in general while describing her activities and ideas about addressing them with science and technology," said Winick. "Many thanks to everyone who helped with her visit."


7.   Upcoming Beam Time Request and Proposal Deadlines

3/14/08 - Beam Time Requests for 3rd Scheduling Period Due

4/01/08 - Macromolecular Crystallography spring proposal deadline

5/01/08 - X-ray/VUV spring proposal deadline

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SSRL Headlines is published electronically monthly to inform SSRL users, sponsors and other interested people about happenings at SSRL. SSRL is a national synchrotron user facility operated by Stanford University for the U.S. Department of Energy Office of Basic Energy Sciences. Additional support for the structural biology program is provided by the DOE Office of Biological and Environmental Research, the NIH National Center for Research Resources and the NIH Institute for General Medical Sciences. Additional information about SSRL and its operation and schedules is available from the SSRL WWW site.

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