PDBsum entry 4qmi

Protein binding

PDB id: 4qmi

Contents

Protein chains

228 a.a.

Waters ×360

PDB id:

4qmi

Name:

Protein binding

Title:

The xmap215 family drives microtubule polymerization using a structurally diverse tog array

Structure:

Cytoskeleton-associated protein 5. Chain: a, b. Fragment: tog domain 4. Synonym: colonic and hepatic tumor overexpressed gene protein, ch- tog. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: chtog, ckap5, kiaa0097. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.177 R-free: 0.215

Authors:

J.C.Fox,A.E.Howard,J.D.Currie,S.L.Rogers,K.C.Slep

Key ref:

J.C.Fox et al. (2014). The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array. Mol Biol Cell, 25, 2375-2392. PubMed id: 24966168 DOI: 10.1091/mbc.E13-08-0501

Date:

16-Jun-14 Release date: 09-Jul-14

Protein chains

Q14008  (CKAP5_HUMAN) -  Cytoskeleton-associated protein 5 from Homo sapiens

Seq: 2032 a.a.

Struc: 228 a.a.

DOI no: 10.1091/mbc.E13-08-0501

Mol Biol Cell 25:2375-2392 (2014)

PubMed id: 24966168

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

J.C.Fox, A.E.Howard, J.D.Currie, S.L.Rogers, K.C.Slep.

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.