PDBsum entry 1w7i

Motor protein

PDB id: 1w7i

Contents

Protein chains

750 a.a.

145 a.a.

Ligands

ADP

Waters ×11

References listed in PDB file

Key reference

Title

Three myosin V structures delineate essential features of chemo-Mechanical transduction.

Authors

P.D.Coureux, H.L.Sweeney, A.Houdusse.

Ref.

EMBO J, 2004, 23, 4527-4537. [DOI no: 10.1038/sj.emboj.7600458]

PubMed id

15510214

Abstract

The molecular motor, myosin, undergoes conformational changes in order to convert chemical energy into force production. Based on kinetic and structural considerations, we assert that three crystal forms of the myosin V motor delineate the conformational changes that myosin motors undergo upon detachment from actin. First, a motor domain structure demonstrates that nucleotide-free myosin V adopts a specific state (rigor-like) that is not influenced by crystal packing. A second structure reveals an actomyosin state that favors rapid release of ADP, and differs from the rigor-like state by a P-loop rearrangement. Comparison of these structures with a third structure, a 2.0 angstroms resolution structure of the motor bound to an ATP analog, illuminates the structural features that provide communication between the actin interface and nucleotide-binding site. Paramount among these is a region we name the transducer, which is composed of the seven-stranded beta-sheet and associated loops and linkers. Reminiscent of the beta-sheet distortion of the F1-ATPase, sequential distortion of this transducer region likely controls sequential release of products from the nucleotide pocket during force generation.

Figure 3.
Figure 3 Cleft closure. (A) The lower and upper 50 kDa subdomains of myosin V MDE have been pulled apart exposing the surface interactions allowing cleft closure. Note (in green on the right) the U50 highly conserved linker that interacts with the HW and HP helices (white on the left) of the L50 subdomain. Switch II (orange) and the strut (pink) are two connectors between the subdomains that help mediate the interactions between these two surfaces and they are shown on both sides. In particular, a hydrophobic residue of switch II (Y439, yellow ball and stick) is a serine or alanine in all myosin II isoforms. This difference may account in part for the difference in the kinetics of cleft closure for the two molecules. (B) A surface CPK representation of the residues involved in this interface is presented in the same orientation as in A). Depending on the conservation in the sequence of these residues in the myosin superfamily, different colors are used (absolutely conserved (green), conservative changes (pale green) and nonconserved (purple)). A yellow star indicates how to reposition the two surfaces to reconstruct the interface.

Figure 6.
Figure 6 The transducer. The transducer is the central region of the motor domain near the nucleotide-binding site that includes the last three strands of the seven-stranded -sheet that undergo distortion between the rigor-like and post-rigor states and the structural elements that accommodate this distortion. Among these elements are the previously studied loop, commonly referred to as loop 1 (residues 184 -191), and the -bulge (pale green) found at the end of the last two -strands. Another of these elements is a linker that follows the HO helix, which provides a pathway of communication to the actin interface. We thus refer to this linker as the HO linker (residues 424 -430); it leads to the fifth -strand that is followed by switch II. Switch I and the P-loop are connected via three parallel -helices that interact with the -sheet. Loop 1 connects the ends of two of these helices (HF and HG). When the -sheet undergoes distortion, these helices rotate and translate relative to each other.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2004, 23, 4527-4537) copyright 2004.