3n2g: Difference between revisions
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==TUBULIN-NSC 613863: RB3 Stathmin-like domain complex== | |||
<StructureSection load='3n2g' size='340' side='right'caption='[[3n2g]], [[Resolution|resolution]] 4.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3n2g]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N2G FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G2N:ETHYL+[(2R)-5-AMINO-2-METHYL-3-PHENYL-1,2-DIHYDROPYRIDO[3,4-B]PYRAZIN-7-YL]CARBAMATE'>G2N</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3n2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n2g OCA], [https://pdbe.org/3n2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n2g RCSB], [https://www.ebi.ac.uk/pdbsum/3n2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n2g ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/D0VWZ0_SHEEP 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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n2/3n2g_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3n2g ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:20675373</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3n2g" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]] | |||
*[[Tubulin 3D Structures|Tubulin 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Ovis aries]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Alfonso C]] | |||
[[Category: Allegro D]] | |||
[[Category: Andreu JM]] | |||
[[Category: Barbier P]] | |||
[[Category: Devred F]] | |||
[[Category: Dorleans A]] | |||
[[Category: Knossow M]] | |||
[[Category: Peyrot V]] | |||
[[Category: Sanz L]] | |||