5jh7

Tubulin-Eribulin complex

spinqualitylabelsall models 5jh7, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jh7 is a 6 chain structure with sequence from Bos taurus, Gallus gallus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Ligands: 03S, 6K9, ACP, CA, GDP, GOL, GTP, IMD, MES, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TBA1B_BOVIN 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 are dynamic polymers built of tubulin dimers that attach in a head-to-tail fashion to form protofilaments, which further associate laterally to form a tube. Asynchronous elongation of individual protofilaments can potentially lead to an altered microtubule-end structure that promotes sudden depolymerization, termed catastrophe [1-4]. However, how the dynamics of individual protofilaments relates to overall growth persistence has remained unclear. Here, we used the microtubule targeting anti-cancer drug Eribulin [5-7] to explore the consequences of stalled protofilament elongation on microtubule growth. Using X-ray crystallography, we first revealed that Eribulin binds to a site on beta-tubulin that is required for protofilament plus-end elongation. Based on the structural information, we engineered a fluorescent Eribulin molecule. We demonstrate that single Eribulin molecules specifically interact with microtubule plus ends and are sufficient to either trigger a catastrophe or induce slow and erratic microtubule growth in the presence of EB3. Interestingly, we found that Eribulin increases the frequency of EB3 comet "splitting," transient events where a slow and erratically progressing comet is followed by a faster comet. This observation possibly reflects the "healing" of a microtubule lattice. Because EB3 comet splitting was also observed in control microtubules in the absence of any drugs, we propose that Eribulin amplifies a natural pathway toward catastrophe by promoting the arrest of protofilament elongation. Termination of Protofilament Elongation by Eribulin Induces Lattice Defects that Promote Microtubule Catastrophes.,Doodhi H, Prota AE, Rodriguez-Garcia R, Xiao H, Custar DW, Bargsten K, Katrukha EA, Hilbert M, Hua S, Jiang K, Grigoriev I, Yang CP, Cox D, Horwitz SB, Kapitein LC, Akhmanova A, Steinmetz MO Curr Biol. 2016 Jul 11;26(13):1713-21. doi: 10.1016/j.cub.2016.04.053. Epub 2016 , Jun 16. PMID:27321995 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stathmin-4 3D structures Tubulin 3D Structures Tubulin tyrosine ligase

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