A TOG:αβ-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase.
Stu2p/XMAP215/Dis1 family proteins are evolutionarily conserved regulatory factors that use αβ-tubulin-interacting tumor overexpressed gene (TOG) domains to catalyze fast microtubule growth. Catalysis requires that these polymerases discriminate between unpolymerized and polymerized forms of αβ-tubulin, but the mechanism by which they do so has remained unclear. Here, we report the structure of the TOG1 domain from Stu2p bound to yeast αβ-tubulin. TOG1 binds αβ-tubulin in a way that excludes equivalent binding of a second TOG domain. Furthermore, TOG1 preferentially binds a curved conformation of αβ-tubulin that cannot be incorporated into microtubules, contacting α- and β-tubulin surfaces that do not participate in microtubule assembly. Conformation-selective interactions with αβ-tubulin explain how TOG-containing polymerases discriminate between unpolymerized and polymerized forms of αβ-tubulin and how they selectively recognize the growing end of the microtubule.
Department of Biophysics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Pelin
P
Ayaz
Xuecheng
X
Ye
Patrick
P
Huddleston
Chad A
CA
Brautigam
Luke M
LM
Rice
D018360:Crystallography, X-Ray; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics; D008870:Microtubules / Q000201:enzymology*; D058105:Polymerization; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D014404:Tubulin / Q000737:chemistry*
D008869:Microtubule-Associated Proteins; C109414:STU2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014404:Tubulin