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Article
Subject Categories: Structural Biology
The EMBO Journal (2008) 27, 244–252, doi:10.1038/sj.emboj.7601937
Published online 29 November 2007
The post-rigor structure of myosin VI and implications for the recovery stroke
Julie Ménétrey1, 2, 4, Paola Llinas1, 2, 4, Jérome Cicolari1, 2, Gaëlle Squires1, 2, Xiaoyan Liu3, Anna Li3, H Lee Sweeney3 and Anne Houdusse1, 2
1 Structural Motility, Institut Curie, Centre de Recherche, Paris, France
2 CNRS UMR144, Paris, France
3 Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

To whom correspondence should be addressed

H Lee Sweeney, Department of Physiology, University of Pennsylvania School of Medicine, A700 Richards Bldg, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA. Tel.: +1 215 898 8727; Fax: +1 215 573 2273; E-mail: Lsweeney@mail.med.upenn.edu
Anne Houdusse, Structural Motility, Institut Curie CNRS, UMR144, 26 rue d'Ulm, 75248 Paris cedex 05, France. Tel.: 33 1 42 34 63 95; Fax: 33 1 42 34 63 82; E-mail: Anne.Houdusse@curie.fr

4 These authors contributed equally to this work

Received 14 September 2007; Accepted 6 November 2007; Published online 29 November 2007.
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.
Keywords: directionality, lever arm, motility, myosin VI, unconventional myosin
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