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Mol Biol Cell August 15, 2014; 25 (16): 2375-92.
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The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array.

Fox JC , Howard AE , Currie JD , Rogers SL , Slep KC .

XMAP215 family members are potent microtubule (MT) polymerases, with mutants displaying reduced MT growth rates and aberrant spindle morphologies. XMAP215 proteins contain arrayed tumor overexpressed gene (TOG) domains that bind tubulin. Whether these TOG domains are architecturally equivalent is unknown. Here we present crystal structures of TOG4 from Drosophila Msps and human ch-TOG. These TOG4 structures architecturally depart from the structures of TOG domains 1 and 2, revealing a conserved domain bend that predicts a novel engagement with α-tubulin. In vitro assays show differential tubulin-binding affinities across the TOG array, as well as differential effects on MT polymerization. We used Drosophila S2 cells depleted of endogenous Msps to assess the importance of individual TOG domains. Whereas a TOG1-4 array largely rescues MT polymerization rates, mutating tubulin-binding determinants in any single TOG domain dramatically reduces rescue activity. Our work highlights the structurally diverse yet positionally conserved TOG array that drives MT polymerization.

PubMed ID: 24966168
PMC ID: PMC4142611
Article link: Mol Biol Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: ckap5 mapre1 med20 tmprss13

Article Images: [+] show captions
References [+] :
Adams, PHENIX: a comprehensive Python-based system for macromolecular structure solution. 2010, Pubmed