Muscle thin-filament structure and regulation. Actin sub-domain movements and the tropomyosin shift modelled from low-angle X-ray diffraction

John M. Squire, Hind A. Al-Khayat, Naoto Yagi

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Abstract

Low-angle X-ray diffraction data from vertebrate muscles in the relaxed state and in the activated state at non-overlap sarcomere lengths have been used to model the relative positions of the four structural sub-domains of the actin monomer and of the tropomyosin strands and to investigate the changes that occur as a result of Ca2+ activation. The model is based on: (i) the published crystal structure of actin-DNase I [W. Kabsch, H. G. Mannherz, D. Suck, E. F. Pai and K. C. Holmes, Nature (London), 1990, 347, 37], (ii) the modelling of the F-actin filament [K. C. Holmes, D. Popp, W. Gebhard and W. Kabsch, Nature (London), 1990, 347, 44], (iii) published measurements of the radii of gyration of F-actin, of F-actin plus tropomyosin and of the tropomyosin strands alone, (iv) our own and published layer-line positions and intensities in the low-angle X-ray diffraction patterns from actin filaments, and (v) sensible steric constraints on actin sub-domain movements and thin filament structure. It is concluded that, even with a four sub-domain structure for actin molecules, the observed low-angle X-ray diffraction patterns cannot be explained without a substantial azimuthal swing (about 20°) of the tropomyosin strands when resting filaments are Ca2+-activated. The direction of this swing on Ca2+-activation is away from a position close to the proposed myosin binding site on actin; a result consistent with the original 'steric blocking model' of actin filament regulation in which tropomyosin position on actin is crucial for regulation of the myosin crossbridge cycle on actin.

Original languageEnglish
Pages (from-to)2717-2726
Number of pages10
JournalJournal of the Chemical Society, Faraday Transactions
Volume89
Issue number15
DOIs
Publication statusPublished - 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

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