4QMH

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

Summary for 4QMH

• Entry DOI: 10.2210/pdb4qmh/pdb
• Related: 4QMI 4QMJ
• Descriptor: LP04448p, SULFATE ION (3 entities in total)
• Functional Keywords: protein binding, tog domain
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 1
• Total formula weight: 26399.59

Authors

Fox, J.C.,Howard, A.E.,Currie, J.D.,Rogers, S.L.,Slep, K.C. (deposition date: 2014-06-16, release date: 2014-07-09, Last modification date: 2024-02-28)

Primary citation

Fox, J.C.,Howard, A.E.,Currie, J.D.,Rogers, S.L.,Slep, K.C.
The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array.
Mol.Biol.Cell, 25:2375-2392, 2014

PubMed Abstract: 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: 24966168
DOI: 10.1091/mbc.E13-08-0501

Experimental method

X-RAY DIFFRACTION (1.652 Å)