SIBYLS help signal target for Anticancer Drugs

Researchers from Genentech in collaboration with SIBYLS beamline scientist, Michal Hammel, used Small Angle X-Ray scattering to learn how an assembly of three proteins works together to transmit signals for cell division. The work reveals new targets for the development of drugs to fight certain types of cancer, including lung, colorectal, and pancreatic.

SAXS used to elucidate mechanism of inner-ear mechanotransduction

Tip link filaments convey force and gate inner-ear hair-cell transduction channels to mediate perception of sound and head movements. Cadherin-23 and protocadherin-15 form tip links through a calcium-dependent interaction of their extracellular domains made of multiple extracellular cadherin (EC) repeats. These repeats are structurally similar, but not identical in sequence, often featuring linkers with conserved…
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Review: Validating Macromolecular Flexibility by SAXS

We bring to your attention a nice review published recently in the European Biophysics Journal describing the theoretical and practical considerations when using SAXS to characterize macromolecular flexibility. >The dynamics of macromolecular conformations are critical to the action of cellular networks. Solution X-ray scattering studies, in combination with macromolecular X-ray crystallography (MX) and nuclear magnetic…
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Mechanism of Activation/Deactivation of Retinoblastoma Protein

SAXS was used to characterize the structural effects of phosphorylation events that modulate the ability of retinoblastoma protein to associate with E2F and other proteins. This work has been published in Genes & Development in the May 8th Advanced Online Articles section. >Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through…
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Structure of XLF-XRCC4 Provides Model for Double Strand Break Repair

DNA double strand break repair via nonhomologous end joining is a critical regulatory function that maintains genomic integrity. One of the major factors involved in this process is the XLF-XRCC4 protein complex. Although mutation of either XLF or XRCC4 leads to defects in break repair, the function of the XLF-XRCC4 complex has remained enigmatic. In…
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Fast SAXS profile computation with Debye formula

FoXS, a new webapp which uses the Debye formula for calculating theoretical scattering profiles, has been made available on the ModBase website. Give it a try to see how it compares to CRYSOL. FoXS is a method for computing a theoretical scattering profile of a structure and fitting of experimental profile. FoXS can be used…
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Recent SAXS structures

SAXS capabilities of the SIBYLS beamline are demonstrated quite nicely in recent papers published in September and October. Datta AB, Hura GL, Wolberger C. “The structure and conformation of Lys63-linked tetraubiquitin.” J Mol Biol. 2009 Oct 9;392(5):1117-24. Epub 2009 Aug 4. Jain R, Hammel M, Johnson RE, Prakash L, Prakash S, Aggarwal AK. “Structural Insights…
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Structure and Flexibility Within Proteins as Identified Through SAXS

In a recent article in the General Physiology and Biophysics we describe an analysis tool using relatively inexpensive small angle X-ray scattering (SAXS) measurements to identify protein flexibility and validate a constructed minimal ensemble of models, which represent highly populated conformations in solution. The resolution of these results is sufficient to address the questions being…
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