Structural model for tubulin recognition and deformation by kinesin-13 microtubule depolymerases

Ana B. Asenjo, Chandrima Chatterjee, Dongyan Tan, Vania DePaoli, William J. Rice, Ruben Diaz-Avalos, Mariena Silvestry, Hernando Sosa

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

To elucidate the structural basis of the mechanism of microtubule depolymerization by kinesin-13s, we analyzed complexes of tubulin and the Drosophila melanogaster kinesin-13 KLP10A by electron microscopy (EM) and fluorescence polarization microscopy. We report a nanometer-resolution (1.1. nm) cryo-EM three-dimensional structure of the KLP10A head domain (KLP10AHD) bound to curved tubulin. We found that binding of KLP10AHD induces a distinct tubulin configuration with displacement (shear) between tubulin subunits in addition to curvature. In this configuration, the kinesin-binding site differs from that in straight tubulin, providing an explanation for the distinct interaction modes of kinesin-13s with the microtubule lattice or its ends. The KLP10AHD-tubulin interface comprises three areas of interaction, suggesting a crossbow-type tubulin-bending mechanism. These areas include the kinesin-13 family conserved KVD residues, and as predicted from the crossbow model, mutating these residues changes the orientation and mobility of KLP10AHDs interacting with the microtubule. Kinesin-13 proteins are microtubule (MT) depolymerases that play a key role in modulating MT dynamics in a variety of cellular processes. How kinesin-13s induce depolymerization, rather than walking along MTs like most other kinesins, is not clear. Structural analysis by Sosa and colleagues shows that binding of the kinesin-13 catalytic domain to tubulin alters its conformation to one that is incompatible with the formation of MTs and instead favors binding of kinesin-13 over that of other kinesin proteins.

Original languageEnglish (US)
Pages (from-to)759-768
Number of pages10
JournalCell Reports
Volume3
Issue number3
DOIs
StatePublished - Feb 22 2013

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this