Poorly Understood Aspects of Striated Muscle Contraction

Figure 6

Structures of the rigor actomyosin complex and the myosin motor domain (S1) at different nucleotide states. (a) High resolution structure of the nucleotide-free actin-myosin- tropomyosin complex as obtained by cryo-electron microscopy (ref. [291], PDB IDs 4a7n, 4a7l, 4a7h, and 4a7f). (b) Ribbon representation of the atomic structure of chicken skeletal muscle myosin S1 fragment (PDB: 2MYS). S1 comprises 843 amino acid residues of the myosin heavy chain and two light chains (RLC and ELC) bound to the C-terminal neck region of the molecule. The central core comprises a seven-stranded β-sheet surrounded by several α helices. Characteristic is the deep cleft in the molecule. The cleft extends from the active site (P-loop, switch 1, and switch 2) to the actin binding elements, which are located in the upper (blue) and lower 50 K (green) domains. The N-terminus is adjacent to the C-terminus forming a protruding SH3-like β-barrel structure (red). The long C-terminal helix (light green) contains two IQ motifs that bind the light chains (ELC and RLC) and acts as a lever arm and conveys together with the converter domain local conformational changes to large movements. Highlighted in red in the insets are the actin binding and nucleotide coordinating loop and switch elements. (c) Conformational rearrangements of the relay helix (unwinding and kinking) and the converter (rotational movement) during the recovery stroke. The recovery stroke drives the detached myosin from the postrigor state to the prepower stroke state. The structures depicted are PDB ID: 2JHR and PDB ID: 1G8X. (d) Structural model for the strong binding start-of-power stroke (ref. [145]). The myosin power stroke is initiated by a transition from a weak-to-strong actin binding state. A rotational movement of the lower 50 K domain from the prepower stroke state (light grey, PDB ID: 2JJ9) enables a rigor-like strong binding geometry of the myosin at the actin interface (shown in brown ribbon representation) without changing the position of the converter domain. The structures were prepared with the PyMOL Molecular Graphics System, Version 1.7.2, Schrödinger, LCC.

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