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The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
Structural highlights
FunctionCKAP5_HUMAN Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles.[1] [2] Publication Abstract from PubMedXMAP215 family members are potent microtubule (MT) polymerases, with mutants displaying reduced MT growth rates and aberrant spindle morphologies. XMAP215 proteins contain arrayed 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 alpha-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. While 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. The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array.,Fox JC, Howard AE, Currie JD, Rogers SL, Slep KC Mol Biol Cell. 2014 Jun 25. pii: mbc.E13-08-0501. PMID:24966168[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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