Details

Autor(en) / Beteiligte

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

Titel

Structural Model for Tubulin Recognition and Deformation by Kinesin-13 Microtubule Depolymerases

Ist Teil von

• Cell reports (Cambridge), 2013-03, Vol.3 (3), p.759-768

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] ► Kinesin-13 tubulin complex structure reported at nanometer resolution ► Inter- and intradimer tubulin heterodimer interfaces are unambiguously identified ► A distinct curved-sheared tubulin conformation is described ► Insights provided into how kinesin-13s recognize and depolymerize microtubule ends 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.