title: How myosin VI coordinates its heads during processive movement.
abstract: A processive molecular motor must coordinate the enzymatic state of its two catalytic domains in order to prevent premature detachment from its track. For myosin V, internal strain produced when both heads of are attached to an actin track prevents completion of the lever arm swing of the lead head and blocks ADP release. However, this mechanism cannot work for myosin VI, since its lever arm positions are reversed. Here, we demonstrate that myosin VI gating is achieved instead by blocking ATP binding to the lead head once it has released its ADP. The structural basis for this unique gating mechanism involves an insert near the nucleotide binding pocket that is found only in class VI myosin. Reverse strain greatly favors binding of ADP to the lead head, which makes it possible for myosin VI to function as a processive transporter as well as an actin-based anchor. While this mechanism is unlike that of any other myosin superfamily member, it bears remarkable similarities to that of another processive motor from a different superfamily--kinesin I.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.forename: Hyokeun
authors.initials: H
authors.lastname: Park
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zong
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Yang
authors.forename: Paul R
authors.initials: PR
authors.lastname: Selvin
authors.forename: Steven S
authors.initials: SS
authors.lastname: Rosenfeld
mesh_terms: D000199:Actins / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000199:Actins; D020409:Molecular Motor Proteins; D010710:Phosphates; C089785:myosin VI; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D018995:Myosin Heavy Chains