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 J. Sosa

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 - 2013

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Kinesin
Structural Models
Tubulin
Microtubules
Depolymerization
Head
Electron microscopy
Polarization Microscopy
Microtubule Proteins
Cryoelectron Microscopy
Fluorescence Polarization
Drosophila melanogaster
Fluorescence Microscopy
Structural analysis
Walking
Conformations
Catalytic Domain
Electron Microscopy
Microscopic examination
Fluorescence

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Structural model for tubulin recognition and deformation by kinesin-13 microtubule depolymerases. / Asenjo, Ana B.; Chatterjee, Chandrima; Tan, Dongyan; DePaoli, Vania; Rice, William J.; Diaz-Avalos, Ruben; Silvestry, Mariena; Sosa, Hernando J.

In: Cell Reports, Vol. 3, No. 3, 2013, p. 759-768.

Research output: Contribution to journalArticle

Asenjo, AB, Chatterjee, C, Tan, D, DePaoli, V, Rice, WJ, Diaz-Avalos, R, Silvestry, M & Sosa, HJ 2013, 'Structural model for tubulin recognition and deformation by kinesin-13 microtubule depolymerases', Cell Reports, vol. 3, no. 3, pp. 759-768. https://doi.org/10.1016/j.celrep.2013.01.030
Asenjo, Ana B. ; Chatterjee, Chandrima ; Tan, Dongyan ; DePaoli, Vania ; Rice, William J. ; Diaz-Avalos, Ruben ; Silvestry, Mariena ; Sosa, Hernando J. / Structural model for tubulin recognition and deformation by kinesin-13 microtubule depolymerases. In: Cell Reports. 2013 ; Vol. 3, No. 3. pp. 759-768.
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AB - 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.

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