Structure. 2014 Aug 5;22(8):1173-83. doi: 10.1016/j.str.2014.06.010

Nucleotide exchange in dimeric MCAK induces longitudinal and lateral stress at microtubule ends to support polymerization

Members of the kinesin-13 subfamily use motor domains in an unconventional fashion to initiate microtubule (MT) depolymerization at MT ends, suggesting unique conformational transitions for lattice engagement, end adaptation, or both. Using hydrogen-deuterium exchange and electron microscopy, we explored conformational changes in free dimeric mitotic centromere-associated kinesin (MCAK) and when bound to a depolymerization intermediate. ATP hydrolysis relaxes the conformation of the dimer, notably in the neck and N-terminal domain. Exchanging ADP in dimeric MCAK with ATP at the MT plus end induces outward curvature in α/β-tubulin, accompanied by a restructuring of the MCAK neck and N terminus, as it returns to a closed state. Reestablishing a closed dimer induces lateral separation of paired tubulin dimers, which may assist in depolymerization. Thus, full-length ADP-MCAK transitions from an open diffusion-competent configuration to a closed state upon plus end-mediated nucleotide exchange, which is mediated by conformational changes in the N-terminal domains of the dimer.

Warning: Use of undefined constant WP_ENV - assumed 'WP_ENV' (this will throw an Error in a future version of PHP) in /nfs/c05/h06/mnt/161631/domains/ on line 65