Loop L5 acts as a conformational latch in the mitotic kinesin Eg5.

ABSTRACT: All members of the kinesin superfamily of molecular motors contain an unusual structural motif consisting of an α-helix that is interrupted by a flexible loop, referred to as L5. We have examined the function of L5 in the mitotic kinesin Eg5 by combining site-directed mutagenesis of L5 with transient state kinetics, molecular dynamics simulations, and docking using cryo electron microscopy density. We find that mutation of a proline residue located at a turn within this loop profoundly slows nucleotide-induced structural changes both at the catalytic site as well as at the microtubule binding domain and the neck linker. Molecular dynamics simulations reveal that this mutation affects the dynamics not only of L5 itself but also of the switch I structural elements that sense ATP binding to t

SUBMITTER: Behnke-Parks WM 

PROVIDER: S-EPMC3037637 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature