3n2g | pdb_00003n2g

TUBULIN-NSC 613863: RB3 Stathmin-like domain complex

spinqualitylabelsall models 3n2g, resolution 4.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n2g is a 5 chain structure with sequence from Ovis aries 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 4Å Ligands: G2N, GDP, GTP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D0VWZ0_SHEEP 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 (By similarity).[RuleBase:RU003505][SAAS:SAAS023123_004_019801] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathmin-like domain of the RB3 protein (T2RB3). GTP hydrolysis following microtubule assembly induces protofilament curvature and disassembly. The conformation of the labile tubulin heterodimers is unknown. One important question is whether free GDP-tubulin dimers are straightened by GTP binding, or if GTP-tubulin is also curved and switches into a straight conformation upon assembly. We have obtained insight into the bending flexibility of tubulin by analyzing the interplay of tubulin-stathmin association with the binding of several small molecule inhibitors to the colchicine domain at the tubulin intradimer interface, combining structural and biochemical approaches. The crystal structures of T2RB3 complexes with the chiral R and S isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl-carba mate, show that their binding site overlaps with colchicine ring A and that both complexes have the same curvature as unliganded T2RB3. The binding of these ligands is incompatible with a straight tubulin structure in microtubules. Analytical ultracentrifugation and binding measurements show that tubulin-stathmin associations (T2RB3, T2Stath) and binding of ligands (R, S, TN-16, or the colchicine analogue MTC) are thermodynamically independent from one another, irrespective of tubulin being bound to GTP or GDP. The fact that the interfacial ligands bind equally well to tubulin dimers or stathmin complexes supports a bent conformation of the free tubulin dimers. It is tempting to speculate that stathmin evolved to recognize curved structures in unassembled and disassembling tubulin, thus regulating microtubule assembly. Stathmin and interfacial microtubule inhibitors recognize a naturally curved conformation of tubulin dimers.,Barbier P, Dorleans A, Devred F, Sanz L, Allegro D, Alfonso C, Knossow M, Peyrot V, Andreu JM J Biol Chem. 2010 Jul 30. PMID:20675373 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stathmin-4 3D structures Tubulin 3D Structures

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