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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.

Pubmed ID: 22904013

Authors

  • Ayaz P
  • Ye X
  • Huddleston P
  • Brautigam CA
  • Rice LM

Journal

Science (New York, N.Y.)

Publication Data

August 17, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM-098543
  • Agency: NIGMS NIH HHS, Id: R01 GM098543

Mesh Terms

  • Crystallography, X-Ray
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm
  • Microtubule-Associated Proteins
  • Microtubules
  • Polymerization
  • Protein Conformation
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins
  • Tubulin