4QMI
The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array
Summary for 4QMI
| Entry DOI | 10.2210/pdb4qmi/pdb |
| Related | 4QMH 4QMJ |
| Descriptor | Cytoskeleton-associated protein 5 (2 entities in total) |
| Functional Keywords | protein binding, tog domain |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: Q14008 |
| Total number of polymer chains | 2 |
| Total formula weight | 53468.11 |
| 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 Cited by 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: 24966168DOI: 10.1091/mbc.E13-08-0501 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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