title: Evidence for cleft closure in actomyosin upon ADP release.
abstract: Structural insights into the interaction of smooth muscle myosin with actin have been provided by computer-based fitting of crystal structures into three-dimensional reconstructions obtained by electron cryomicroscopy, and by mapping of structural and dynamic changes in the actomyosin complex. The actomyosin structures determined in the presence and absence of MgADP differ significantly from each other, and from all crystallographic structures of unbound myosin. Coupled to a complex movement ( approximately 34 A) of the light chain binding domain upon MgADP release, we observed a approximately 9 degrees rotation of the myosin motor domain relative to the actin filament, and a closure of the cleft that divides the actin binding region of the myosin head. Cleft closure is achieved by a movement of the upper 50 kDa region, while parts of the lower 50 kDa region are stabilized through strong interactions with actin. This model supports a mechanism in which binding of MgATP at the active site opens the cleft and disrupts the interface, thereby releasing myosin from actin.
authors: The Burnham Institute, La Jolla, California 92037, USA.
authors: N
authors: N
authors: Volkmann
authors: D
authors: D
authors: Hanein
authors: G
authors: G
authors: Ouyang
authors: K M
authors: KM
authors: Trybus
authors: D J
authors: DJ
authors: DeRosier
authors: S
authors: S
authors: Lowey
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D000205:Actomyosin / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D009130:Muscle, Smooth; D009218:Myosins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D018583:Pliability; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012399:Rotation
chemical_list: D000199:Actins; D020409:Molecular Motor Proteins; D000244:Adenosine Diphosphate; D000205:Actomyosin; D009218:Myosins