title: Structural model for tubulin recognition and deformation by kinesin-13 microtubule depolymerases.
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.
authors: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Ana B
authors: AB
authors: Asenjo
authors: Chandrima
authors: C
authors: Chatterjee
authors: Dongyan
authors: D
authors: Tan
authors: Vania
authors: V
authors: DePaoli
authors: William J
authors: WJ
authors: Rice
authors: Ruben
authors: R
authors: Diaz-Avalos
authors: Mariena
authors: M
authors: Silvestry
authors: Hernando
authors: H
authors: Sosa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D004331:Drosophila melanogaster / Q000737:chemistry / Q000378:metabolism*; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; D021122:Protein Subunits; D014404:Tubulin; C481339:KLP10A protein, Drosophila; D016547:Kinesins