title: The structural basis of myosin V processive movement as revealed by electron cryomicroscopy.
abstract: The processive motor myosin V has a relatively high affinity for actin in the presence of ATP and, thus, offers the unique opportunity to visualize some of the weaker, hitherto inaccessible, actin bound states of the ATPase cycle. Here, electron cryomicroscopy together with computer-based docking of crystal structures into three-dimensional (3D) reconstructions provide the atomic models of myosin V in both weak and strong actin bound states. One structure shows that ATP binding opens the long cleft dividing the actin binding region of the motor domain, thus destroying the strong binding actomyosin interface while rearranging loop 2 as a tether. Nucleotide analogs showed a second new state in which the lever arm points upward, in a prepower-stroke configuration (lever arm up) bound to actin before phosphate release. Our findings reveal how the structural elements of myosin V work together to allow myosin V to step along actin for multiple ATPase cycles without dissociating.
authors.affiliation: The Program of Cell Adhesion, The Burnham Institute, La Jolla, California 92037, USA.
authors.forename: Niels
authors.initials: N
authors.lastname: Volkmann
authors.forename: HongJun
authors.initials: H
authors.lastname: Liu
authors.forename: Larnele
authors.initials: L
authors.lastname: Hazelwood
authors.forename: Elena B
authors.initials: EB
authors.lastname: Krementsova
authors.forename: Susan
authors.initials: S
authors.lastname: Lowey
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Trybus
authors.forename: Dorit
authors.initials: D
authors.lastname: Hanein
mesh_terms: D000199:Actins / Q000502:physiology* / Q000648:ultrastructure*; D000205:Actomyosin / Q000502:physiology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000378:metabolism; D000818:Animals; D020285:Cryoelectron Microscopy / Q000379:methods*; D051379:Mice; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D024701:Myosin Type V / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D017434:Protein Structure, Tertiary
chemical_list: D000199:Actins; D020409:Molecular Motor Proteins; D000266:Adenylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D000205:Actomyosin; D024701:Myosin Type V