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Nat Commun. 2017 Jul 10;8(1):70. doi: 10.1038/s41467-017-00091-9.

Insight into microtubule disassembly by kinesin-13s from the structure of Kif2C bound to tubulin.

Author information

1
Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
2
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
3
Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. chunguangwang@tongji.edu.cn.
4
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France. benoit.gigant@i2bc.paris-saclay.fr.

Abstract

Kinesin-13s are critical microtubule regulators which induce microtubule disassembly in an ATP dependent manner. To clarify their mechanism, we report here the crystal structure of a functional construct of the kinesin-13 Kif2C/MCAK in an ATP-like state and bound to the αβ-tubulin heterodimer, a complex mimicking the species that dissociates from microtubule ends during catalytic disassembly. Our results picture how Kif2C stabilizes a curved tubulin conformation. The Kif2C α4-L12-α5 region undergoes a remarkable 25° rotation upon tubulin binding to target the αβ-tubulin hinge. This movement leads the β5a-β5b motif to interact with the distal end of β-tubulin, whereas the neck and the KVD motif, two specific elements of kinesin-13s, target the α-tubulin distal end. Taken together with the study of Kif2C mutants, our data suggest that stabilization of a curved tubulin is an important contribution to the Kif2C mechanism.Kinesin-13s are microtubule depolymerizing enzymes. Here the authors present the crystal structure of a DARPin fused construct comprising the short neck region and motor domain of kinesin-13 in complex with an αβ-tubulin heterodimer, which shows that kinesin-13 functions by stabilizing a curved tubulin conformation.

PMID:
28694425
PMCID:
PMC5503940
DOI:
10.1038/s41467-017-00091-9
[Indexed for MEDLINE]
Free PMC Article

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