Muscle contraction involves the cyclic interaction of the myosin cross-bridges with the actin filament, which is coupled to steps in the hydrolysis of ATP1. While bound to actin each cross-bridge undergoes a conformational change, often referred to as the “power stroke”2, which moves the actin filament past the myosin filaments; this is associated with the release of the products of ATP hydrolysis and a stronger binding of myosin to actin. The association of a new ATP molecule weakens the binding again, and the attached cross-bridge rapidly dissociates from actin. The nucleotide is then hydrolysed, the conformational change reverses, and the myosin cross-bridge reattaches to actin. X-ray crystallography has determined the structural basis of the power stroke, but it is still not clear why the binding of actin weakens that of the nucleotide and vice versa. Here we describe, by fitting atomic models of actin and the myosin cross-bridge into high-resolution electron cryo-microscopy three-dimensional reconstructions, the molecular basis of this linkage. The closing of the actin-binding cleft when actin binds is structurally coupled to the opening of the nucleotide-binding pocket.
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The authors declare that they have no competing financial interests.
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We thank J. Frank for discussions, support and encouragement, and P. Bele for technical assistance during image processing.
Supplementary Information: This Zip file contains 6 files, 5 are in pdb format and one is in Brix format. 3actin.pdb: F-actin model, showing 3 actin monomers, axis.pdb: orientation of upper 50K domain rotation axis (depicted as pseudo-Ca-chain), motor_domain.pdb: myosin model excluding the residues of the upper 50K domain , original_upper_50K_domain.pdb: upper 50K domain in its crystallographic position (Rayment et al., 1993), upper_50K_domain.pdb: upper 50K domain in its rotated, strong binding position, em_density.brix: reconstructed density from present EM study. For further information on PDB format please see http://www.rcsb.org/pdb/index.html (ZIP 1499 kb)
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