6ew0

Cryo-EM structure of GDP-microtubule co-polymerised with doublecortin and supplemented with Taxol

Loading... Status: waiting for Mol* initialization Structural highlights 6ew0 is a 12 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GDP, GTP, MG, TA1 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. [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 Microtubules form from longitudinally and laterally assembling tubulin alpha-beta dimers. The assembly induces strain in tubulin, resulting in cycles of microtubule catastrophe and regrowth. This 'dynamic instability' is governed by GTP hydrolysis that renders the microtubule lattice unstable, but it is unclear how. We used a human microtubule nucleating and stabilizing neuronal protein, doublecortin, and high-resolution cryo-EM to capture tubulin's elusive hydrolysis intermediate GDP*Pi state, alongside the prehydrolysis analog GMPCPP state and the posthydrolysis GDP state with and without an anticancer drug, Taxol. GTP hydrolysis to GDP*Pi followed by Pi release constitutes two distinct structural transitions, causing unevenly distributed compressions of tubulin dimers, thereby tightening longitudinal and loosening lateral interdimer contacts. We conclude that microtubule catastrophe is triggered because the lateral contacts can no longer counteract the strain energy stored in the lattice, while reinforcement of the longitudinal contacts may support generation of force. The role of tubulin-tubulin lattice contacts in the mechanism of microtubule dynamic instability.,Manka SW, Moores CA Nat Struct Mol Biol. 2018 Jul 2. pii: 10.1038/s41594-018-0087-8. doi:, 10.1038/s41594-018-0087-8. PMID:29967541 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tubulin

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