title: Magnesium regulates ADP dissociation from myosin V.
abstract: Processivity in myosin V is mediated through the mechanical strain that results when both heads bind strongly to an actin filament, and this strain regulates the timing of ADP release. However, what is not known is which steps that lead to ADP release are affected by this mechanical strain. Answering this question will require determining which of the several potential pathways myosin V takes in the process of ADP release and how actin influences the kinetics of these pathways. We have addressed this issue by examining how magnesium regulates the kinetics of ADP release from myosin V and actomyosin V. Our data support a model in which actin accelerates the release of ADP from myosin V by reducing the magnesium affinity of a myosin V-MgADP intermediate. This is likely a consequence of the structural changes that actin induces in myosin to release phosphate. This effect on magnesium affinity provides a plausible explanation for how mechanical strain can alter this actin-induced acceleration. For actomyosin V, magnesium release follows phosphate release and precedes ADP release. Increasing magnesium concentration to within the physiological range would thus slow both the ATPase activity and the velocity of movement of this motor.
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, FOT 1020, 1530 3rd Ave. South, Birmingham, AL 35294, USA. stevensr@uab.edu
authors.forename: Steven S
authors.initials: SS
authors.lastname: Rosenfeld
authors.forename: Anne
authors.initials: A
authors.lastname: Houdusse
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
mesh_terms: D000205:Actomyosin / Q000737:chemistry / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism*; D001665:Binding Sites; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism; D009068:Movement; D024701:Myosin Type V / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation
chemical_list: D020409:Molecular Motor Proteins; D000244:Adenosine Diphosphate; D000205:Actomyosin; D024701:Myosin Type V; D008274:Magnesium