A cool look at the structural changes in kinesin motor domains

Abstract

Recently, several 3D images of kinesin-family motor domains interacting with microtubules have been obtained by analysis of electron microscope images of frozen hydrated complexes at much higher resolutions (9-12 Å) than in previous reports (15-30 Å). The high-resolution maps show a complex interaction interface between kinesin and tubulin, in which kinesin's switch II helix α4 is a central feature. Differences due to the presence of ADP, as compared with ATP analogues, support previously determined crystal structures of kinesins alone in suggesting that α4 is part of a pathway linking the nucleotide-binding site and the neck that connects to cargo. A 3D structure of the microtubule-bound Kar3 motor domain in a nucleotide-free state has revealed dramatic changes not yet reported for any crystal structure, including melting of the switch II helix, that may be part of the mechanism by which information is transmitted. A nucleotide-dependent movement of helix α6, first seen in crystal structures of Kif1a, appears to bring it into contact with tubulin and may provide another communication link. A microtubule-induced movement of loop L7 and a related distortion of the central β-sheet, detected only in the empty state, may also send a signal to the region of the motor core that interacts with the neck. Earlier images of a kinesin-1 dimer in the empty state, showing a close interaction between the two motor heads, can now be interpreted in terms of a communication route from the active site of the directly bound head via its central β-sheet to the tethered head.