Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly [electronic resource].
- Published
- Washington, D.C. : United States. Dept. of Energy. Office of Science, 2015.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy - Physical Description
- pages E3,806-E3,815 : digital, PDF file
- Additional Creators
- University of Wisconsin--Madison, United States. Department of Energy. Office of Science, National Institutes of Health (U.S.), National Science Foundation (U.S.), and United States. Department of Energy. Office of Scientific and Technical Information
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- Free-to-read Unrestricted online access
- Summary
- The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report in this paper that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility. Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. Finally, in addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies.
- Report Numbers
- E 1.99:1213724
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- Other Subject(s)
- Note
- Published through SciTech Connect.
07/06/2015.
Proceedings of the National Academy of Sciences of the United States of America 112 29 ISSN 0027-8424 AM
Keenan C. Taylor; Massimo Buvoli; Elif Nihal Korkmaz; Ada Buvoli; Yuqing Zheng; Nathan T. Heinze; Qiang Cui; Leslie A. Leinwand; Ivan Rayment. - Funding Information
- W-31-109-ENG-38
R21 HL111237
R01 GM29090
NSF-CHE1300209
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