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A comparison of muscle thin filament models obtained from electron microscopy reconstructions and low-angle X-ray fibre diagrams from non-overlap muscle

DOI: 10.1016/j.jsb.2006.02.020 DOI Help
PMID: 16793285 PMID Help

Authors: Katrina J.v. Poole (Arbeitsgruppe Biophysik, Max Planck Institut für medizinische Forschung, 69120 Heidelberg, Germany.) , Michael Lorenz (Arbeitsgruppe Biophysik, Max Planck Institut für medizinische Forschung, 69120 Heidelberg, Germany.) , Gwyndaf Evans (Diamond Light Source) , Gerd Rosenbaum (Argonne National Laboratory, USA.) , Alnoor Pirani (Boston University School of Medicine, USA.) , Roger Craig (University of Massachusetts Medical School, USA.) , Larry S. Tobacman (University of Illinois at Chicago, USA.) , William Lehman (Boston University School of Medicine, USA.) , Kenneth C. Holmes (Max Planck Institut für medizinische Forschung, Germany)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Structural Biology , VOL 155 (2) , PAGES 273 - 284

State: Published (Approved)
Published: August 2006

Abstract: The regulation of striated muscle contraction involves changes in the interactions of troponin and tropomyosin with actin thin filaments. In resting muscle, myosin-binding sites on actin are thought to be blocked by the coiled–coil protein tropomyosin. During muscle activation, Ca2+ binding to troponin alters the tropomyosin position on actin, resulting in cyclic actin–myosin interactions that accompany muscle contraction. Evidence for this steric regulation by troponin–tropomyosin comes from X-ray data [Haselgrove, J.C., 1972. X-ray evidence for a conformational change in the actin-containing filaments of verterbrate striated muscle. Cold Spring Habor Symp. Quant. Biol. 37, 341–352; Huxley, H.E., 1972. Structural changes in actin and myosin-containing filaments during contraction. Cold Spring Habor Symp. Quant. Biol. 37, 361–376; Parry, D.A., Squire, J.M., 1973. Structural role of tropomyosin in muscle regulation: analysis of the X-ray diffraction patterns from relaxed and contracting muscles. J. Mol. Biol. 75, 33–55] and electron microscope (EM) data [Spudich, J.A., Huxley, H.E., Finch, J., 1972. Regulation of skeletal muscle contraction. II. Structural studies of the interaction of the tropomyosin–troponin complex with actin. J. Mol. Biol. 72, 619–632; O’Brien, E.J., Gillis, J.M., Couch, J., 1975. Symmetry and molecular arrangement in paracrystals of reconstituted muscle thin filaments. J. Mol. Biol. 99, 461–475; Lehman, W., Craig, R., Vibert, P., 1994. Ca(2+)-induced tropomyosin movement in Limulus thin filaments revealed by three-dimensional reconstruction. Nature 368, 65–67] each with its own particular strengths and limitations. Here we bring together some of the latest information from EM analysis of single thin filaments from Pirani et al. [Pirani, A., Xu, C., Hatch, V., Craig, R., Tobacman, L.S., Lehman, W. (2005). Single particle analysis of relaxed and activated muscle thin filaments. J. Mol. Biol. 346, 761–772], with synchrotron X-ray data from non-overlapped muscle fibres to refine the models of the striated muscle thin filament. This was done by incorporating current atomic-resolution structures of actin, tropomyosin, troponin and myosin subfragment-1. Fitting these atomic coordinates to EM reconstructions, we present atomic models of the thin filament that are entirely consistent with a steric regulatory mechanism. Furthermore, fitting the atomic models against diffraction data from skinned muscle fibres, stretched to non-overlap to preclude crossbridge binding, produced very similar results, including a large Ca2+-induced shift in tropomyosin azimuthal location but little change in the actin structure or apparent alteration in troponin position.

Journal Keywords: Tropomyosin; Actin; Thin filament structure; Striated muscle activation; Calcium activation; Steric blocking; Myosin crossbridge; Crossbridge binding

Subject Areas: Biology and Bio-materials

Facility: NSLS