Conformation of the troponin core complex in the thin filaments of skeletal muscle during relaxation and active contraction.

Journal of Molecular Biology
Andrea C KnowlesYin-Biao Sun

Abstract

Contraction of skeletal and cardiac muscles is regulated by Ca(2+) binding to troponin in the actin-containing thin filaments, leading to an azimuthal movement of tropomyosin around the filament that uncovers the myosin binding sites on actin. Here, we use polarized fluorescence to determine the orientation of the C-terminal lobe of troponin C (TnC) in skeletal muscle cells as a step toward elucidating the molecular mechanism of troponin-mediated regulation. Assuming, as shown by X-ray crystallography, that this lobe of TnC is part of a well-defined troponin domain called the IT arm, we show that the coiled coil formed by troponin components I and T makes an angle of about 55° with the thin filament axis in relaxed muscle, in contrast with previous models based on electron microscopy in which this angle is close to 0°. The E helix of TnC makes an angle of about 45° with the thin filament axis. Both the IT coiled coil and the TnC E helix tilt by about 10° on muscle activation. By combining in situ measurements of the orientation of the IT arm and regulatory domain of troponin, which together form the troponin core complex, with published intermolecular distances between thin filament components, we derive models of thin filament...Continue Reading

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Citations

Dec 18, 2013·Archives of Biochemistry and Biophysics·Ian M RobertsonBrian D Sykes
Oct 16, 2012·The Journal of Biological Chemistry·Devanand Kowlessur, Larry S Tobacman
Mar 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Luca FusiMalcolm Irving
Aug 8, 2014·Journal of Molecular and Cellular Cardiology·Ivanka SevrievaYin-Biao Sun
Sep 17, 2015·Chemical Biology & Drug Design·William SchlechtWenji Dong
Nov 12, 2013·Biophysical Journal·Peter M Kekenes-HuskeyJ Andrew McCammon
Jan 9, 2020·Journal of Biomolecular NMR·Ian M RobertsonBrian D Sykes
Jul 2, 2016·Journal of Forensic Sciences·Samah F IbrahimDina S Abd El-Fatah
Apr 29, 2019·Journal of Muscle Research and Cell Motility·Steven Marston, Juan Eiros Zamora
Apr 9, 2020·Frontiers in Physiology·Alfredo Jesus López-DávilaRobert Stehle

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