Structural highlights
6bjc is a 14 chain structure with sequence from Human and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Gene: | TPX2, C20orf1, C20orf2, DIL2, HCA519 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[TBA1B_PIG] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [TPX2_HUMAN] Spindle assembly factor. Required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules. Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation.[1] [2] [TBB_PIG] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Publication Abstract from PubMed
During mitosis and meiosis, microtubule (MT) assembly is locally upregulated by the chromatin-dependent Ran-GTP pathway. One of its key targets is the MT-associated spindle assembly factor TPX2. The molecular mechanism of how TPX2 stimulates MT assembly remains unknown because structural information about the interaction of TPX2 with MTs is lacking. Here, we determine the cryo-electron microscopy structure of a central region of TPX2 bound to the MT surface. TPX2 uses two flexibly linked elements ('ridge' and 'wedge') in a novel interaction mode to simultaneously bind across longitudinal and lateral tubulin interfaces. These MT-interacting elements overlap with the binding site of importins on TPX2. Fluorescence microscopy-based in vitro reconstitution assays reveal that this interaction mode is critical for MT binding and facilitates MT nucleation. Together, our results suggest a molecular mechanism of how the Ran-GTP gradient can regulate TPX2-dependent MT formation.
Structural insight into TPX2-stimulated microtubule assembly.,Zhang R, Roostalu J, Surrey T, Nogales E Elife. 2017 Nov 9;6. pii: e30959. doi: 10.7554/eLife.30959. PMID:29120325[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bird AW, Hyman AA. Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A. J Cell Biol. 2008 Jul 28;182(2):289-300. doi: 10.1083/jcb.200802005. PMID:18663142 doi:http://dx.doi.org/10.1083/jcb.200802005
- ↑ Moss DK, Wilde A, Lane JD. Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase. J Cell Sci. 2009 Mar 1;122(Pt 5):644-55. doi: 10.1242/jcs.037259. Epub 2009 Feb, 10. PMID:19208764 doi:http://dx.doi.org/10.1242/jcs.037259
- ↑ Zhang R, Roostalu J, Surrey T, Nogales E. Structural insight into TPX2-stimulated microtubule assembly. Elife. 2017 Nov 9;6. pii: e30959. doi: 10.7554/eLife.30959. PMID:29120325 doi:http://dx.doi.org/10.7554/eLife.30959
