3cb2: Difference between revisions
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==Crystal structure of human gamma-tubulin bound to GDP== | |||
<StructureSection load='3cb2' size='340' side='right'caption='[[3cb2]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3cb2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CB2 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]] 2.303Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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=3cb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cb2 OCA], [https://pdbe.org/3cb2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cb2 RCSB], [https://www.ebi.ac.uk/pdbsum/3cb2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cb2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TBG1_HUMAN TBG1_HUMAN] Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation. | |||
== 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/cb/3cb2_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=3cb2 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
GTP-dependent microtubule polymerization dynamics are required for cell division and are accompanied by domain rearrangements in the polymerizing subunit, alphabeta-tubulin. Two opposing models describe the role of GTP and its relationship to conformational change in alphabeta-tubulin. The allosteric model posits that unpolymerized alphabeta-tubulin adopts a more polymerization-competent conformation upon GTP binding. The lattice model posits that conformational changes occur only upon recruitment into the growing lattice. Published data support a lattice model, but are largely indirect and so the allosteric model has prevailed. We present two independent solution probes of the conformation of alphabeta-tubulin, the 2.3 A crystal structure of gamma-tubulin bound to GDP, and kinetic simulations to interpret the functional consequences of the structural data. These results (with our previous gamma-tubulin:GTPgammaS structure) support the lattice model by demonstrating that major domain rearrangements do not occur in eukaryotic tubulins in response to GTP binding, and that the unpolymerized conformation of alphabeta-tubulin differs significantly from the polymerized one. Thus, geometric constraints of lateral self-assembly must drive alphabeta-tubulin conformational changes, whereas GTP plays a secondary role to tune the strength of longitudinal contacts within the microtubule lattice. alphabeta-Tubulin behaves like a bent spring, resisting straightening until forced to do so by GTP-mediated interactions with the growing microtubule. Kinetic simulations demonstrate that resistance to straightening opposes microtubule initiation by specifically destabilizing early assembly intermediates that are especially sensitive to the strength of lateral interactions. These data provide new insights into the molecular origins of dynamic microtubule behavior. | |||
The lattice as allosteric effector: structural studies of alphabeta- and gamma-tubulin clarify the role of GTP in microtubule assembly.,Rice LM, Montabana EA, Agard DA Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5378-83. Epub 2008 Apr 3. PMID:18388201<ref>PMID:18388201</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3cb2" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Tubulin 3D Structures|Tubulin 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Agard DA]] | |||
[[Category: Agard | [[Category: Montabana EA]] | ||
[[Category: Montabana | [[Category: Rice LM]] | ||
[[Category: Rice | |||
Latest revision as of 15:25, 30 August 2023
Crystal structure of human gamma-tubulin bound to GDPCrystal structure of human gamma-tubulin bound to GDP
Structural highlights
FunctionTBG1_HUMAN Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation. 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 PubMedGTP-dependent microtubule polymerization dynamics are required for cell division and are accompanied by domain rearrangements in the polymerizing subunit, alphabeta-tubulin. Two opposing models describe the role of GTP and its relationship to conformational change in alphabeta-tubulin. The allosteric model posits that unpolymerized alphabeta-tubulin adopts a more polymerization-competent conformation upon GTP binding. The lattice model posits that conformational changes occur only upon recruitment into the growing lattice. Published data support a lattice model, but are largely indirect and so the allosteric model has prevailed. We present two independent solution probes of the conformation of alphabeta-tubulin, the 2.3 A crystal structure of gamma-tubulin bound to GDP, and kinetic simulations to interpret the functional consequences of the structural data. These results (with our previous gamma-tubulin:GTPgammaS structure) support the lattice model by demonstrating that major domain rearrangements do not occur in eukaryotic tubulins in response to GTP binding, and that the unpolymerized conformation of alphabeta-tubulin differs significantly from the polymerized one. Thus, geometric constraints of lateral self-assembly must drive alphabeta-tubulin conformational changes, whereas GTP plays a secondary role to tune the strength of longitudinal contacts within the microtubule lattice. alphabeta-Tubulin behaves like a bent spring, resisting straightening until forced to do so by GTP-mediated interactions with the growing microtubule. Kinetic simulations demonstrate that resistance to straightening opposes microtubule initiation by specifically destabilizing early assembly intermediates that are especially sensitive to the strength of lateral interactions. These data provide new insights into the molecular origins of dynamic microtubule behavior. The lattice as allosteric effector: structural studies of alphabeta- and gamma-tubulin clarify the role of GTP in microtubule assembly.,Rice LM, Montabana EA, Agard DA Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5378-83. Epub 2008 Apr 3. PMID:18388201[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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