The conformational cycle of kinesin

The stepping mechanism of kinesin can be thought of as a programme of confo rmational changes. ME briefly review protein chemical, electron microscopic and transient kinetic evidence for conformational changes, and working fi om this evidence, outline a model for the mechanism. In the model, both kin esin heads initially trap Mg.ADP. Microtubule binding releases ADP from one head only (the trailing head). Subsequent ATP binding and hydrolysis by th e trailing head progressively accelerate attachment of the leading head, Ly positioning it closer to its next site. Once attached, the leading head re leases its ADP and exerts a sustained pull on the tr ailing head. The rate of closure of the molecular gate which traps ADP on the trailing head gover ns its detachment rate. A speculative but crucial coordinating feature is t hat this rate is strain sensitive, slowing down under negative strain and a ccelerating under positive strain.