Category: Science Highlights

Designing and defining dynamic protein cage nanoassemblies in solution

Central challenges in the design of large and dynamic macromolecular assemblies for synthetic biology lie in developing effective methods for testing design strategies and their outcomes, including comprehensive assessments of solution behavior. The authors of this paper created and validated an advanced design of a 600-kDa protein homododecamer that self-assembles into a symmetric tetrahedral cage.…
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Formation of repressive complex in the mammalian circadian clock is demoted by the secondary pocket of CRY1

In this paper, the authors show that CRY1, a protein coding gene that activates circadian gene expression and metabolic states and circadian oscillators, binds directly to the PAS domain core of CLOCK:BMAL1. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24 hr periodicity of gene expression. Integrative modeling and solution X-ray scattering…
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Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor

Apoptosis-inducing factor (AIF) is critical for mitochondrial respiratory complex biogenesis and for mediating necroptotic parthanatos; these functions are seemingly regulated by enigmatic allosteric switching driven by NADH charge-transfer complex (CTC) formation. In this paper the authors define molecular pathways linking AIF’s active site to allosteric switching regions by characterizing dimer-permissive mutants using small-angle X-ray scattering…
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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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Exploring the Repeat Protein Universe through Computational Protein Design

The facilities and staff at the SYBILS beamline contributed to this breakthrough study exploring the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Naturally occurring proteins–chains of amino acids that fold into functional, three-dimensional shapes–are believed to represent just a small fraction of the universe of…
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Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody

The facilities and staff at the SIBYLS beamline contributed to this recent structural study of a human antibody that is able to neutralize Marburg and Ebola viruses. >The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ…
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Protein flexibility linked to severity of Lou Gerhig’s disease

SAXS and MX data collected at SIBYLS enabled insights into protein flexibility in one of the proteins involved in Lou Gerigh’s disease. The results were recently published in PNAS and have been highlighted by [Today At Berkeley Lab](http://newscenter.lbl.gov/2014/10/13/berkeley-lab-and-scripps-research-institute-scientists-link-als-progression-to-increased-protein-instability/) and and [Daily Cal](http://www.dailycal.org/2014/10/16/berkeley-lab-scripps-institute-propose-cause-als/). >Protein framework alterations in heritable Cu, Zn superoxide dismutase (SOD) mutants cause misassembly…
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SAXS and EM used to determine structure of Gold Nanopartice

Recently in Science: >Structure determination of gold nanoparticles (AuNPs) is necessary for understanding their physical and chemical properties, but only one AuNP larger than 1 nanometer in diameter [a 102-gold atom NP (Au102NP)] has been solved to atomic resolution. Whereas the Au102NP structure was determined by x-ray crystallography, other large AuNPs have proved refractory to…
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