Print Email Facebook Twitter The depolymerase activity of MCAK shows a graded response to Aurora B kinase phosphorylation through allosteric regulation Title The depolymerase activity of MCAK shows a graded response to Aurora B kinase phosphorylation through allosteric regulation Author McHugh, Toni (The University of Edinburgh) Zou, Juan (The University of Edinburgh) Volkov, V. (TU Delft BN/Marileen Dogterom Lab) Bertin, Aurélie (Universite Pierre et Marie Curie (UPMC)) Talapatra, Sandeep K. (The University of Edinburgh) Rappsilber, Juri (Technical University of Berlin; The University of Edinburgh) Dogterom, A.M. (TU Delft BN/Bionanoscience) Welburn, Julie P.I. (The University of Edinburgh) Department BN/Bionanoscience Date 2019 Abstract Kinesin-13 motors regulate precise microtubule dynamics and limit microtubule length throughout metazoans by depolymerizing microtubule ends. Recently, the kinesin-13 motor family member MCAK (also known Kif2C) has been proposed to undergo large conformational changes during its catalytic cycle, as it switches from being in solution to being bound to microtubules. Here, we reveal that MCAK has a compact conformation in solution through crosslinking and electron microscopy experiments. When MCAK is bound to the microtubule ends, it adopts an extended conformation with the N-terminus and neck region of MCAK interacting with the microtubule. Interestingly, the region of MCAK that interacts with the microtubule is the region phosphorylated by Aurora B and contains an end binding (EB) protein-binding motif. The level of phosphorylation of the N-terminus results in a graded microtubule depolymerase activity. Here, we show that the N-terminus of MCAK forms a platform to integrate Aurora B kinase downstream signals and in response fine-tunes its depolymerase activity during mitosis. We propose that this allosteric control mechanism allows decoupling of the N-terminus from the motor domain of MCAK to allow MCAK depolymerase activity at kinetochores. Subject Aurora BMCAKMicrotubulesPhosphorylation To reference this document use: http://resolver.tudelft.nl/uuid:fd2b6e20-9ad3-4706-ad25-3ae642051bc0 DOI https://doi.org/10.1242/jcs.228353 ISSN 0021-9533 Source Journal of Cell Science, 132 (4) Part of collection Institutional Repository Document type journal article Rights © 2019 Toni McHugh, Juan Zou, V. Volkov, Aurélie Bertin, Sandeep K. Talapatra, Juri Rappsilber, A.M. Dogterom, Julie P.I. Welburn Files PDF jcs228353.full.pdf 4.78 MB Close viewer /islandora/object/uuid:fd2b6e20-9ad3-4706-ad25-3ae642051bc0/datastream/OBJ/view