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 language | English (US) |
|---|---|
| Pages (from-to) | 759-768 |
| Number of pages | 10 |
| Journal | Cell Reports |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Structural model for tubulin recognition and deformation by kinesin-13 microtubule depolymerases
AU - Asenjo, Ana B.
AU - Chatterjee, Chandrima
AU - Tan, Dongyan
AU - DePaoli, Vania
AU - Rice, William J.
AU - Diaz-Avalos, Ruben
AU - Silvestry, Mariena
AU - Sosa, Hernando J.
PY - 2013
Y1 - 2013
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84875806836&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875806836&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2013.01.030
DO - 10.1016/j.celrep.2013.01.030
M3 - Article
C2 - 23434508
AN - SCOPUS:84875806836
VL - 3
SP - 759
EP - 768
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -