Welcome to BioCAT

The APS shut down on April 17, 2023 for an upgrade. During this APS-U dark period the BioCAT beamline is unavailable for x-ray experiments. We anticipate resuming user experiments in late 2024/early 2025.

Find out more about: the APS-U; SAXS experiments during the APS-U dark period; Fiber experiments during the APS-U dark period.

Science Highlights

Titin-Based Force Modulates Cardiac Thick and Thin Filaments

The Frank-Starling Law of the Heart states that the heart’s stroke volume increases with greater preload due to increased venous return, allowing the heart to adapt to varying circulatory demands. At the molecular level, increasing preload increases sarcomere length (SL), which alters structures w ithin the sarcomere that are correlated to increased calcium sensitivity upon activation. The titin protein, spanning the half-sarcomere acts as a spring in the I-band, applies a SL-dependent passive force on the myosin containing thick filaments changing its structure and functional properties. Altered titin-based forces play a crucial role in the etiology of many cardiomyopathies; however, the disease state obscures titin’s role, impeding therapeutic solutions. The authors studied titin’s specific role and concluded that reducing titin-based forces blunts structural changes in both thick and thin filaments while leaving the length-dependent OFF-to-ON transition mechanism intact, indicating a clear role for titin in the Frank-Starling mechanism.

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How hydrophobicity, side chains, and salt affect the dimensions of disordered proteins

Understanding the driving forces behind stability of denatured state ensembles (DSE’s) and intrinsically disordered proteins (IDP’s) is central to a number of unresolved questions in bimolecular thermodynamics regarding protein folding pathways and foldability, thermodynamic stability, aggregation and misfolding. Researchers at the University of Chicago and Notre Dame used temperature-controlled size-exclusion chromatography-coupled SAXS (SEC-SAXS) and NMR to examine how temperature and solvent ionic strength influences the solution structure(s) of the N-terminal domain of pertactin (PNt). PNt is a valuable model system from a fundamental biophysical point of view, as the full-length 539-residue pertactin folds into a parallel β-helix but the 334 N-terminal residues do not and instead behave as a highly expanded, intrinsically disordered chain.

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Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads

Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. Here the authors used combination of mechanics and small-angle X-ray diffraction to study the effects of immediate and selective removal of the particular domains of fast MyBP-C on sarcomere structure and function in permeabilized skeletal muscle. They concluded that the MyBP-C domains play an important role in contractile performance.

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BioCAT Plans for the APS-U Dark Period

The APS shut down on April 17, 2023 for a major year-long upgrade, the “APS-U” project. There is no user access to the APS during this “dark period”. We anticipate that BioCAT will resume user experiments in late 2024/early 2025. We continue to help support experiments by our users at other beamlines, including sending BioCAT staff to other beamlines to help with some of the more complicated experiments, until operations resume at BioCAT.

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Register for ACA SAS Workshop

BioCAT is helping organize an introductory small angle scattering workshop at the 2024 ACA Annual Meeting in Denver CO. The workshop will introduce both the theory of the method and best practices common to the field and will include lectures and a selection of hands-on practical exercises from leading experts in the field. The course will take place on July 7th, 2024.

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BioCAT scientist gets grant to study inherited cardiac conditions

BioCAT scientist Weikang Ma was awarded a five year $2 million grant from the NIH to study inherited cardiac conditions.

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