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==Structural Basis of Tubulin Recruitment and Assembly by Microtubule Polymerases with Tumor Overexpressed Gene (TOG) Domain Arrays== | |||
<StructureSection load='6mzf' size='340' side='right' caption='[[6mzf]], [[Resolution|resolution]] 4.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6mzf]] is a 28 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895], [http://en.wikipedia.org/wiki/Lack1 Lack1] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MZF 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> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6mze|6mze]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SKLU-Cont10078 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=226302 LACK1])</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=6mzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mzf OCA], [http://pdbe.org/6mzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mzf RCSB], [http://www.ebi.ac.uk/pdbsum/6mzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mzf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/TBA1A_PIG TBA1A_PIG]] 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/TBB_PIG TBB_PIG]] 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 == | |||
XMAP215/Stu2/Alp14 proteins accelerate microtubule plus-end polymerization by recruiting tubulins via arrays of tumor overexpressed gene (TOG) domains, yet their mechanism remains unknown. Here, we describe the biochemical and structural basis for TOG arrays in recruiting and polymerizing tubulins. Alp14 binds four tubulins via dimeric TOG1-TOG2 subunits, in which each domain exhibits a distinct exchange rate for tubulin. X-ray structures revealed square-shaped assemblies composed of pseudo-dimeric TOG1-TOG2 subunits assembled head-to-tail, positioning four unpolymerized tubulins in a polarized wheel-like configuration. Crosslinking and electron microscopy show Alp14-tubulin forms square assemblies in solution, and inactivating their interfaces destabilize this organization without influencing tubulin binding. An X-ray structure determined using approach to modulate tubulin polymerization revealed an unfurled assembly, in which TOG1-TOG2 uniquely bind to two polymerized tubulins. Our findings suggest a new microtubule polymerase model in which TOG arrays recruit tubulins by forming square assemblies that then unfurl, facilitating their concerted polymerization into protofilaments. | |||
Structural basis of tubulin recruitment and assembly by microtubule polymerases with tumor overexpressed gene (TOG) domain arrays.,Nithianantham S, Cook BD, Beans M, Guo F, Chang F, Al-Bassam J Elife. 2018 Nov 13;7. pii: 38922. doi: 10.7554/eLife.38922. PMID:30422110<ref>PMID:30422110</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6mzf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacillus coli migula 1895]] | |||
[[Category: Lack1]] | |||
[[Category: Sus scrofa]] | |||
[[Category: Al-Bassam, J]] | [[Category: Al-Bassam, J]] | ||
[[Category: Nithianantham, S]] | [[Category: Nithianantham, S]] | ||
[[Category: And wheel-like assembly]] | |||
[[Category: Cell cycle]] | |||
[[Category: Heat repeat]] | |||
[[Category: Microtubule]] | |||
[[Category: Microtubule polymerase]] | |||
[[Category: Tog array]] | |||
[[Category: Tubulin]] | |||
[[Category: Tubulin polymerization]] |
Revision as of 23:38, 2 December 2018
Structural Basis of Tubulin Recruitment and Assembly by Microtubule Polymerases with Tumor Overexpressed Gene (TOG) Domain ArraysStructural Basis of Tubulin Recruitment and Assembly by Microtubule Polymerases with Tumor Overexpressed Gene (TOG) Domain Arrays
Structural highlights
Function[TBA1A_PIG] 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. [TBB_PIG] 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 PubMedXMAP215/Stu2/Alp14 proteins accelerate microtubule plus-end polymerization by recruiting tubulins via arrays of tumor overexpressed gene (TOG) domains, yet their mechanism remains unknown. Here, we describe the biochemical and structural basis for TOG arrays in recruiting and polymerizing tubulins. Alp14 binds four tubulins via dimeric TOG1-TOG2 subunits, in which each domain exhibits a distinct exchange rate for tubulin. X-ray structures revealed square-shaped assemblies composed of pseudo-dimeric TOG1-TOG2 subunits assembled head-to-tail, positioning four unpolymerized tubulins in a polarized wheel-like configuration. Crosslinking and electron microscopy show Alp14-tubulin forms square assemblies in solution, and inactivating their interfaces destabilize this organization without influencing tubulin binding. An X-ray structure determined using approach to modulate tubulin polymerization revealed an unfurled assembly, in which TOG1-TOG2 uniquely bind to two polymerized tubulins. Our findings suggest a new microtubule polymerase model in which TOG arrays recruit tubulins by forming square assemblies that then unfurl, facilitating their concerted polymerization into protofilaments. Structural basis of tubulin recruitment and assembly by microtubule polymerases with tumor overexpressed gene (TOG) domain arrays.,Nithianantham S, Cook BD, Beans M, Guo F, Chang F, Al-Bassam J Elife. 2018 Nov 13;7. pii: 38922. doi: 10.7554/eLife.38922. PMID:30422110[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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