The Central Role of the Tail in Switching Off Myosin II in Cells

Abstract

23Myosin II is a motor protein playing an essential role in cell motility. The molecule can exist as a 24polymer that pulls on actin to generate motion, or as an inactive monomer with a compact 25 structure, in which its tail is folded and its two heads interact with each other. This conformation 26 functions in cells as an energy-conserving storage and transport molecule. The mechanism of 27 inhibition is not fully understood. We have carried out a 3D reconstruction of the switched-off form 28revealing for the first time multiple interactions between the tail and the two heads that trap ATP 29 hydrolysis products, block actin binding, obstruct head phosphorylation, and prevent filament 30formation. Blocking these essential features of myosin function can explain the high degree of 31 inhibition of the folded form of myosin, serving its energy-conserving, storage function in cells. The 32 structure also suggests a mechanism for unfolding when activated by phosphorylation. 33 34