PDBsum entry 2vb6

Motor protein

PDB id: 2vb6

Contents

Protein chains

724 a.a.

145 a.a.

Ligands

ADP-BEF

Metals

_MG

_CA ×4

Waters ×237

References listed in PDB file

Key reference

Title

The post-Rigor structure of myosin VI and implications for the recovery stroke.

Authors

J.Ménétrey, P.Llinas, J.Cicolari, G.Squires, X.Liu, A.Li, H.L.Sweeney, A.Houdusse.

Ref.

EMBO J, 2008, 27, 244-252. [DOI no: 10.1038/sj.emboj.7601937]

PubMed id

18046460

Abstract

Myosin VI has an unexpectedly large swing of its lever arm (powerstroke) that optimizes its unique reverse direction movement. The basis for this is an unprecedented rearrangement of the subdomain to which the lever arm is attached, referred to as the converter. It is unclear at what point(s) in the myosin VI ATPase cycle rearrangements in the converter occur, and how this would effect lever arm position. We solved the structure of myosin VI with an ATP analogue (ADP.BeF3) bound in its nucleotide-binding pocket. The structure reveals that no rearrangement in the converter occur upon ATP binding. Based on previously solved myosin structures, our structure suggests that no reversal of the powerstroke occurs during detachment of myosin VI from actin. The structure also reveals novel features of the myosin VI motor that may be important in maintaining the converter conformation during detachment from actin, and other features that may promote rapid rearrangements in the structure following actin detachment that enable hydrolysis of ATP.

Figure 1.
Figure 1 Important features of the myosin VI motor. (A) The different elements of the myosin VI motor are shown in the rigor-like myosin VI structure (Ménétrey et al, 2005). The motor domain is composed of four subdomains (Nter, U50, L50 and the converter). The converter (green) is the most mobile of these and is directly linked to the lever arm. In myosin VI, the converter interacts with a unique inserted structural element (insert 2; purple). This redirects the lever arm in the opposite direction from plus-end myosins. The central beta-sheet (gray and blue) is the major component of the transducer, which can adopt differently twisted conformations depending on the nucleotide- and actin-binding states of the motor. There are three nucleotide-binding elements: P-loop, switch I and switch II. Rotation of the converter is controlled by the rearrangements of the relay (yellow) and the SH1-helix (red). (B) Diagram illustrating the converter (green) and the lever arm (purple for the insert 2-CaM-binding region and cyan for the IQ-CaM) position in three states of the myosin VI motor cycle. The motor domain is composed of an SH3 domain (black ball) and four subdomains (N-terminal (Nter, gray), upper 50 kDa (U50, blue), lower 50 kDa (L50, light gray) and converter). The relay (yellow) and SH1-helix (red) are two connectors of the motor that direct the rotation of the converter. The powerstroke corresponds to the large (11 nm) movement of the lever arm between the pre-powerstroke (PPS, 2V26) and rigor state (2BKH), during which the converter both rotates and alters its conformation. ATP binding in the rigor state induces rearrangements in the motor to detach the motor from actin and produce the post-rigor state. To optimize the powerstroke, no reversal of the lever arm movement should occur upon ATP binding and myosin detachment from actin. However, it is not clear that this can be accomplished for myosin VI, since it is unclear what happens to the converter conformation and lever arm position following ATP binding.

Figure 2.
Figure 2 The post-rigor state of myosin VI. (A) The myosin VI post-rigor structure is compared to that in the rigor-like state (right). The motors are oriented as if they are bound to a vertical actin filament (black arrow). Note the position of the lever arm, which is very similar in the rigor-like and post-rigor states. (B) On the left, porcine myosin VI in the post-rigor state (red) is compared with the myosin VI rigor-like state (black) after superposition of the L50 subdomains. Note the difference in the position of the Nter and U50 subdomains. The actin-binding cleft is more open in the post-rigor state (red) compared with the rigor-like state (black). On the right, three different post-rigor state structures are superimposed (chicken myosin V in black, Dictyostelium myosin II in gray and porcine myosin VI in red). Note that the positions of their subdomains are quite similar.

The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2008, 27, 244-252) copyright 2008.