Myosin VI is an actin-based motor that moves backwards

• Published in: Nature (London) Vol. 401; no. 6752; pp. 505 - 508
• Main Authors: Sweeney, H. Lee, Wells, Amber L, Lin, Abel W, Chen, Li-Qiong, Safer, Daniel, Cain, Shane M, Hasson, Tama, Carragher, Bridget O, Milligan, Ronald A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 30.09.1999; Nature Publishing Group
• Subjects: Actins - physiology; Actins - ultrastructure; Adenosine diphosphate; Adenosine Diphosphate - metabolism; Amino acids; Analytical, structural and metabolic biochemistry; Animals; ATP; Biological and medical sciences; Biomechanical Phenomena; Calmodulin - metabolism; Cells; Contractile proteins; Converters; Cryoelectron Microscopy; Crystal structure; Filaments; Fundamental and applied biological sciences. Psychology; Holoproteins; Humans; Levers; Microscopy; Molecular biology; Molecular Motor Proteins; Motors; Movements; Myosin; Myosin Heavy Chains - genetics; Myosin Heavy Chains - physiology; Myosin Heavy Chains - ultrastructure; Proteins; Recombinant Proteins - metabolism; Swine; Molecular motion; Molecular structure; Contractile protein; Microfilament; Molecular interaction; Electron microscopy; Biological activity; Pig; Vertebrata; Image analysis; Mammalia; Actin; Myosin; Artiodactyla; Ungulata; Conformation
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/46835

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules, all characterized myosin motors move towards the barbed (+) end of actin filaments. Crystal structures of myosin II (refs 3,4,5,6) have shown that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-binding helix and associated light chains. The lever arm further amplifies the motions of the converter domain into large directed movements. Here we report that myosin VI, an unconventional myosin, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.