Structural Molecular Biology

The SMB macromolecular crystallography (MC) program is a major experimental driver for structural biology research, serving the needs of a large number of academic and biotech groups working in this area, particularly in the Western U.S, developing, providing and supporting cutting-edge technologies for a wide-range of user applications.

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X-ray scattering from partially ordered arrays of biomolecules typically provides low-resolution (≥ 7-10 Å) structural information under biologically relevant conditions. Studies are relatively fast, require small quantities of material and are well-suited for time resolved measurements. Applications range from conformational change to folding intermediate studies.

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Metal ions have key roles in biological structure and function - from being active sites of many enzymes to having roles in signaling pathways and being key elements of cancer chemotherapies and disease-related biological malfunctions. Synchrotron x-ray spectroscopies are a key tool in determining the geometric and electronic structure of metal centers.

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A Metals in Structural Biology workshop will be held on September 25, 2019 as part of our Annual Users' Meeting.

Metals in protein environments can confer unique reactivity, and challenging chemistry often involves complex metallocofactors. Synchrotron-based techniques enable experiments that closely measure and monitor metal active site geometry and protein structure. For redox-active crystal samples on which X-ray diffraction data is obtained, parallel spectroscopic methods are being increasingly used to investigate whether the observed 3-dimensional structure is in an enzymatically active or inactive state, as well as whether the metal oxidation state has been altered in the X-ray beam. In this workshop on Metals in Structural Biology we will emphasize the use of spectroscopic methods (electron paramagnetic resonance (EPR), UV-vis, and X-ray spectroscopy methods), with a break out session to explore development of EPR methods for single crystals.

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A new Multi-Technique Proposal mechanism has been created for projects that require the use of two or more scientific techniques available at SSRL (both x-ray and electron based). The pilot proposal mechanism will initially cover Small Angle X-ray Scattering, Macromolecular Crystallography and Cryo-Electron Microscopy. A goal is to expand the mechanism in its permanent phase to include additional techniques available at LCLS and spectroscopy and imaging methods at SSRL.

The new pilot proposals will require a thorough justification for the requirement of using two or more techniques. The proposals will be reviewed by an ad hoc Proposal Review Panel comprised of members from the SSRL SMB and Cryo-EM PRPs. The new proposal template is now available and the first deadline for submission will be July 1.

To get started:  Log into User Portal  -> Select SSRL as the Facility -> Choose Submit Structural Biology-related Multi-Technique Proposal from SSRL Proposals pulldown menu.