title: Cargo binding induces dimerization of myosin VI.
abstract: Although myosin VI has properties that would allow it to function optimally as a dimer, full-length myosin VI exists as a monomer in isolation. Based on the ability of myosin VI monomers to dimerize when held in close proximity, we postulated that cargo binding normally regulates dimerization of myosin VI. We tested this hypothesis by expressing a known dimeric cargo adaptor protein of myosin VI, optineurin, and the myosin VI-binding segment from a monomeric cargo adaptor protein, Dab2. In the presence of these adaptor proteins, full-length myosin VI has ATPase properties of a dimer, appears as a dimer in electron micrographs, and moves processively on actin filaments. The results support a model in which cargo binding exposes internal dimerization sequences within full-length myosin VI. Because, unexpectedly, a monomeric fragment of Dab2 triggers dimerization, it would appear that myosin VI is designed to function as a dimer in cells.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Phichith
authors.forename: Mirko
authors.initials: M
authors.lastname: Travaglia
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zong
authors.forename: Daniel
authors.initials: D
authors.lastname: Safer
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D019281:Dimerization; D008854:Microscopy, Electron; D008958:Models, Molecular; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D020349:Surface Plasmon Resonance; D013552:Swine; D025521:Tumor Suppressor Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D025521:Tumor Suppressor Proteins; C089785:myosin VI; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains