Introduction to Muscle Contraction, Part 2
Crystallographic studies show two distinct structural states for myosin S1: the open or end conformation which is characterized by the absence of nucleotide (rigor); and the closed or beginning state, which is favored by binding ATP or the products complex (ADP.Π). Myosin transports actin by switching between these two states. Open and closed refer to the status of the ATP binding site which extends from the 50K upper domain across to the 50K lower domain. This in turn is coupled to the rotation of a C-terminal lever arm. In the closed form the lever arm is at the beginning of the power stroke whereas in the open form it is at the end of the power stoke. The preference for open or closed is also controlled by binding to actin. We hypothesize that the closed state binds only weakly to actin. On this basis we can correlate the structural states with the Lymn-Taylor cycle.
Starting from an actin-myosin complex at the end of the power stroke, the binding of ATP brings about rapid closure of the cleft and concomitant release from actin. The closed state hydrolyses ATP to ADP.? without attaching to actin. Thereafter, the rebinding of myosin in the closed or beginning conformation of the products complex to actin opens the cleft to facilitate release of the ?-phosphate. Release of phosphate induces an isomerisation to the open end conformation since it is the presence of the ?-phosphate which stabilizes the closed form. The isomerisation results in large changes of angle of the lever arm (at the distal part of the myosin head). Since the S1 is strongly attached to actin at this stage this results in a 12nm transport of actin past myosin.