Rigor to post-rigor transition in myosin V: link between the dynamics and the supporting architecture.
The detachment kinetics from actin upon ATP binding is a key step in the reaction cycle of myosin V. We show that a network of residues, constituting the allostery wiring diagram (AWD), that trigger the rigor (R) to post-rigor (PR) transition, span key structural elements from the ATP and actin-binding regions. Several of the residues are in the 33 residue helix (H18), P loop, and switch I. Brownian dynamics simulations show that a hierarchy of kinetically controlled local structural changes leads to the opening of the "cleft" region, resulting in the detachment of the motor domain from actin. Movements in switch I and P loop facilitate changes in the rest of the motor domain, in particular the rotation of H18, whose stiffness within the motor domain is crucial in the R --> PR transition. The finding that residues in the AWD also drive the kinetics of the R --> PR transition shows how the myosin architecture regulates the allosteric movements during the reaction cycle.
Tehver
Riina
R
Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA.
Thirumalai
D
D
D000199:Actins / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D004023:Dictyostelium; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D024701:Myosin Type V / Q000737:chemistry*; D009218:Myosins / Q000737:chemistry; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D000199:Actins; D000255:Adenosine Triphosphate; D024701:Myosin Type V; D009218:Myosins