Switch 1 Opens on Strong Binding to Actin

Abstract

The 50K domain of the myosin cross bridge is split into two subdomains (upper and lower) by the major cleft that connects the actin binding site with the nucleotide binding site. A number of lines of experimental evidence now point to the major cleft closing on strong binding of the cross bridge to actin. In particular, our recent high resolution (14Å) cryo EFTEM images show that most of the 50K upper domain is involved in this movement. However, the switch 1 element of the nucleotide binding site is anchored in the 50K upper domain so that the strong binding to actin will lead to a 5-l0Å movement of switch 1. Thus strong binding to actin moves switch 1. The movement of switch 1 opens the nucleotide binding site. This movement is quite distinct from the opening of switch 2, which is connected with the movement of the lever arm during the power stroke. The possibility that switch 1 moves (opens) on actin binding suggests new mechanisms for the initiation of the power stroke and for the release of ADP and phosphate during the cross bridge cycle.