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==Cryo EM density of microtubule assembled from human TUBB3-D417H mutant==
==Cryo EM density of microtubule assembled from human TUBB3-D417H mutant==
<StructureSection load='5ij9' size='340' side='right' caption='[[5ij9]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
<SX load='5ij9' size='340' side='right' viewer='molstar' caption='[[5ij9]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5ij9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IJ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IJ9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5ij9]] 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=5IJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IJ9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ij0|5ij0]]</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>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ij9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ij9 OCA], [http://pdbe.org/5ij9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ij9 RCSB], [http://www.ebi.ac.uk/pdbsum/5ij9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ij9 ProSAT]</span></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=5ij9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ij9 OCA], [https://pdbe.org/5ij9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ij9 RCSB], [https://www.ebi.ac.uk/pdbsum/5ij9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ij9 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/TBB3_HUMAN TBB3_HUMAN]] Congenital fibrosis of extraocular muscles;Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TBA1B_HUMAN TBA1B_HUMAN]] 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. [[http://www.uniprot.org/uniprot/TBB3_HUMAN TBB3_HUMAN]] 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. TUBB3 plays a critical role in proper axon guidance and mantainance.<ref>PMID:20074521</ref> 
[https://www.uniprot.org/uniprot/TBA1B_HUMAN TBA1B_HUMAN] 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. Here, we purify and characterize tubulin heterodimers that have human beta-tubulin isotype III (TUBB3), as well as heterodimers with one of two beta-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.


Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends.,Ti SC, Pamula MC, Howes SC, Duellberg C, Cade NI, Kleiner RE, Forth S, Surrey T, Nogales E, Kapoor TM Dev Cell. 2016 Apr 4;37(1):72-84. doi: 10.1016/j.devcel.2016.03.003. PMID:27046833<ref>PMID:27046833</ref>
==See Also==
 
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ij9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</SX>
[[Category: Cade, N I]]
[[Category: Homo sapiens]]
[[Category: Duellberg, C]]
[[Category: Large Structures]]
[[Category: Forth, S]]
[[Category: Cade NI]]
[[Category: Howes, S C]]
[[Category: Duellberg C]]
[[Category: Kapoor, T M]]
[[Category: Forth S]]
[[Category: Kleiner, R E]]
[[Category: Howes SC]]
[[Category: Nogales, E]]
[[Category: Kapoor TM]]
[[Category: Pamula, M C]]
[[Category: Kleiner RE]]
[[Category: Surrey, T]]
[[Category: Nogales E]]
[[Category: Ti, S C]]
[[Category: Pamula MC]]
[[Category: Human]]
[[Category: Surrey T]]
[[Category: Hydrolysis]]
[[Category: Ti SC]]
[[Category: Microtubule]]
[[Category: Mutant tubulin]]
[[Category: Structural protein]]

Latest revision as of 15:34, 6 March 2024

Cryo EM density of microtubule assembled from human TUBB3-D417H mutantCryo EM density of microtubule assembled from human TUBB3-D417H mutant

5ij9, resolution 3.70Å

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OCA
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