Abstract
The rigor to post-rigor transition in myosin, a consequence of ATP binding, plays an essential role in the Lymn–Taylor functional cycle because it results in the dissociation of the actomyosin complex after the powerstroke. On the basis of the X-ray structures of myosin V, we have developed a new normal mode superposition model for the transition path between the two states. Rigid-body motions of the various subdomains and specific residues at the subdomain interfaces are key elements in the transition. The allosteric communication between the nucleotide binding site and the U50/L50 cleft is shown to result from local changes due to ATP binding, which induce large amplitude motions that are encoded in the structure of the protein. The triggering event is the change in the interaction of switch I and the P-loop, which is stabilized by ATP binding. The motion of switch I, which is a relatively rigid element of the U50 subdomain, leads directly to a partial opening of the U50/L50 cleft; the latter is expected to weaken the binding of myosin to actin. The calculated transition path demonstrates the nature of the subdomain coupling and offers an explanation for the mutual exclusion of ATP and actin binding. The mechanism of the uncoupling of the converter from the motor head, an essential part of the transition, is elucidated. The origin of the partial untwisting of the central β-sheet in the rigor to post-rigor transition is described.
Highlights
Motion is one of the hallmarks of life
Myosins are molecular motor proteins that interact with actin filaments to perform a wide range of cellular functions
A fundamental question concerns the mechanism by which the local structural changes due to adenosine triphosphate (ATP) binding, hydrolysis, and products release can generate the large myosin changes of conformation required for this cycle
Summary
Motion is one of the hallmarks of life. Myosins are molecular motor proteins that use ATP to power interactions with actin filaments, so as to generate force and directed movement. This model proposes that small conformational changes in the motor domain are coupled to and amplified by the lever arm, whose position is controlled by the rotation of the converter subdomain Given such coupling, it is likely that the induced motion is diffusive and corresponds to transitions between different conformational states which are stabilized by the nature of the ligand; i.e., no ligand; ATP; ADP?Pi; ADP. It is likely that the induced motion is diffusive and corresponds to transitions between different conformational states which are stabilized by the nature of the ligand; i.e., no ligand; ATP; ADP?Pi; ADP This implies that the motor domain cycles through well-defined, though fluctuating, structural states which differ in their nucleotide and actin binding affinities. The release of ADP from the trailing head is slightly accelerated and that from the leading head is significantly slowed down [11,12]
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