4QMH

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

4QMH の概要

• エントリーDOI: 10.2210/pdb4qmh/pdb
• 関連するPDBエントリー: 4QMI 4QMJ
• 分子名称: LP04448p, SULFATE ION (3 entities in total)
• 機能のキーワード: protein binding, tog domain
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26399.59

構造登録者

Fox, J.C.,Howard, A.E.,Currie, J.D.,Rogers, S.L.,Slep, K.C. (登録日: 2014-06-16, 公開日: 2014-07-09, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.652 Å)