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Structural transitions in myosin and the origin of contractile force in muscle
Author(s) -
Harrington W. F.,
Ueno H.
Publication year - 1987
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360260010
Subject(s) - myosin , chemistry , biophysics , crossbridge , myosin head , conformational change , actin , cleavage (geology) , protein filament , isometric exercise , hinge , muscle contraction , crystallography , myosin light chain kinase , stereochemistry , anatomy , biochemistry , biology , physiology , mechanical engineering , paleontology , fracture (geology) , engineering
Force generation in actively contracting muscle very likely involves a structural transition in each cycling cross‐bridge while it is attached to actin. Two different types of force‐generating mechanisms are discussed in this paper: (1) the force‐generating event results from a change in the effective angle of the myosin head (S‐1 subunit) and (2) a conformational change in the α‐helical S‐2 region of the crossbridge occurs when this portion of the bridge is released from the thick‐filament surface. This process causes shortening in S‐2 and produces force. Evidence supporting mechanism 2 has been obtained from recent studies of actively contracting muscle fibers and of isolated myosin rod subfragments using an enzyme‐ (chymotrypsin) probe technique to detect and pinpoint local melting within the α‐helical structure. The kinetics of proteolysis and the site of cleavage were determined at various temperatures (5 to 40°C) by electrophoresis of digestion products on SDS gels. We found the cleavage sites to be localized in a restricted segment of S‐2 spanning the LMM/HMM hinge region (64,000–90,000 M r /polypeptide chain from the C‐terminus of the myosin rod). The cleavage rate constant for activated muscle fibers in the presence of an ATP‐regenerating system was about 100 times larger at each temperature than that for rigor or relaxed muscle fibers, and it showed a marked increase in magnitude with increasing temperature. Comparative plots of the apparent rate constant for cleavage within the S‐2 hinge domain and the isometric force generated by active fibers vs MgATP concentration gave closely similar profiles, suggesting a close coupling between the conformational transitions within the S‐2 hinge domain and contractile force when the cross‐bridges undergo cycling.