PDBsum entry 4qmi

Protein binding

PDB id: 4qmi

Contents

Protein chains

228 a.a.

Waters ×360

References listed in PDB file

Key reference

• Title: The xmap215 family drives microtubule polymerization using a structurally diverse tog array.
• Authors: J.C.Fox, A.E.Howard, J.D.Currie, S.L.Rogers, K.C.Slep.
• Ref.: Mol Biol Cell, 2014, 25, 2375-2392. [DOI no: 10.1091/mbc.E13-08-0501]
• PubMed id: 24966168

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.