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The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array

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 un...

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Autores principales: Fox, Jaime C., Howard, Amy E., Currie, Joshua D., Rogers, Stephen L., Slep, Kevin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142611/
https://www.ncbi.nlm.nih.gov/pubmed/24966168
http://dx.doi.org/10.1091/mbc.E13-08-0501
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author Fox, Jaime C.
Howard, Amy E.
Currie, Joshua D.
Rogers, Stephen L.
Slep, Kevin C.
author_facet Fox, Jaime C.
Howard, Amy E.
Currie, Joshua D.
Rogers, Stephen L.
Slep, Kevin C.
author_sort Fox, Jaime C.
collection PubMed
description 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.
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spelling pubmed-41426112014-10-30 The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array Fox, Jaime C. Howard, Amy E. Currie, Joshua D. Rogers, Stephen L. Slep, Kevin C. Mol Biol Cell Articles 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. The American Society for Cell Biology 2014-08-15 /pmc/articles/PMC4142611/ /pubmed/24966168 http://dx.doi.org/10.1091/mbc.E13-08-0501 Text en © 2014 Fox et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Fox, Jaime C.
Howard, Amy E.
Currie, Joshua D.
Rogers, Stephen L.
Slep, Kevin C.
The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
title The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
title_full The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
title_fullStr The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
title_full_unstemmed The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
title_short The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
title_sort xmap215 family drives microtubule polymerization using a structurally diverse tog array
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142611/
https://www.ncbi.nlm.nih.gov/pubmed/24966168
http://dx.doi.org/10.1091/mbc.E13-08-0501
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