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


ABSTRACT: 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 ?/?-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.

SUBMITTER: Burns KM 

PROVIDER: S-EPMC4386277 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Burns Kyle M KM   Wagenbach Mike M   Wordeman Linda L   Schriemer David C DC  

Structure (London, England : 1993) 20140724 8


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, notab  ...[more]

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