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5jh7

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Tubulin-Eribulin complex

Structural highlights

5jh7 is a 6 chain structure with sequence from Bos taurus, Gallus gallus 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 2.25Å
Ligands:	, , , , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TBA1B_BOVIN 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 PubMed

Microtubules are dynamic polymers built of tubulin dimers that attach in a head-to-tail fashion to form protofilaments, which further associate laterally to form a tube. Asynchronous elongation of individual protofilaments can potentially lead to an altered microtubule-end structure that promotes sudden depolymerization, termed catastrophe [1-4]. However, how the dynamics of individual protofilaments relates to overall growth persistence has remained unclear. Here, we used the microtubule targeting anti-cancer drug Eribulin [5-7] to explore the consequences of stalled protofilament elongation on microtubule growth. Using X-ray crystallography, we first revealed that Eribulin binds to a site on beta-tubulin that is required for protofilament plus-end elongation. Based on the structural information, we engineered a fluorescent Eribulin molecule. We demonstrate that single Eribulin molecules specifically interact with microtubule plus ends and are sufficient to either trigger a catastrophe or induce slow and erratic microtubule growth in the presence of EB3. Interestingly, we found that Eribulin increases the frequency of EB3 comet "splitting," transient events where a slow and erratically progressing comet is followed by a faster comet. This observation possibly reflects the "healing" of a microtubule lattice. Because EB3 comet splitting was also observed in control microtubules in the absence of any drugs, we propose that Eribulin amplifies a natural pathway toward catastrophe by promoting the arrest of protofilament elongation.

Termination of Protofilament Elongation by Eribulin Induces Lattice Defects that Promote Microtubule Catastrophes.,Doodhi H, Prota AE, Rodriguez-Garcia R, Xiao H, Custar DW, Bargsten K, Katrukha EA, Hilbert M, Hua S, Jiang K, Grigoriev I, Yang CP, Cox D, Horwitz SB, Kapitein LC, Akhmanova A, Steinmetz MO Curr Biol. 2016 Jul 11;26(13):1713-21. doi: 10.1016/j.cub.2016.04.053. Epub 2016 , Jun 16. PMID:27321995^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Doodhi H, Prota AE, Rodriguez-Garcia R, Xiao H, Custar DW, Bargsten K, Katrukha EA, Hilbert M, Hua S, Jiang K, Grigoriev I, Yang CP, Cox D, Horwitz SB, Kapitein LC, Akhmanova A, Steinmetz MO. Termination of Protofilament Elongation by Eribulin Induces Lattice Defects that Promote Microtubule Catastrophes. Curr Biol. 2016 Jul 11;26(13):1713-21. doi: 10.1016/j.cub.2016.04.053. Epub 2016 , Jun 16. PMID:27321995 doi:http://dx.doi.org/10.1016/j.cub.2016.04.053

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jh7"

@@ Line 3: / Line 3: @@
 <StructureSection load='5jh7' size='340' side='right'caption='[[5jh7]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jh7]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JH7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JH7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jh7]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] 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=5JH7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JH7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=03S:METHANESULFONIC+ACID'>03S</scene>, <scene name='pdbligand=6K9:(1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-AMINO-2-HYDROXYPROPYL]-21-METHOXY-14-METHYL-8,15-DIMETHYLIDENE-2,19,30,34,37,39,40,41-OCTAOXANONACYCLO[24.9.2.1~3,32~.1~3,33~.1~6,9~.1~12,16~.0~18,22~.0~29,36~.0~31,35~]HENTETRACONTAN-24-ONE+(NON-PREFERRED+NAME)'>6K9</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Stmn4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), TTL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=03S:METHANESULFONIC+ACID'>03S</scene>, <scene name='pdbligand=6K9:(1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-AMINO-2-HYDROXYPROPYL]-21-METHOXY-14-METHYL-8,15-DIMETHYLIDENE-2,19,30,34,37,39,40,41-OCTAOXANONACYCLO[24.9.2.1~3,32~.1~3,33~.1~6,9~.1~12,16~.0~18,22~.0~29,36~.0~31,35~]HENTETRACONTAN-24-ONE+(NON-PREFERRED+NAME)'>6K9</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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://proteopedia.org/fgij/fg.htm?mol=5jh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jh7 OCA], [http://pdbe.org/5jh7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jh7 RCSB], [http://www.ebi.ac.uk/pdbsum/5jh7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jh7 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=5jh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jh7 OCA], [https://pdbe.org/5jh7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jh7 RCSB], [https://www.ebi.ac.uk/pdbsum/5jh7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jh7 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN]] 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/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref>  [[http://www.uniprot.org/uniprot/TBB2B_BOVIN TBB2B_BOVIN]] 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).
+[https://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN] 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 ==
@@ Line 24: / Line 24: @@
 *[[Tubulin 3D Structures|Tubulin 3D Structures]]
 *[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]]
-*[[User:Alisa Cario|User:Alisa Cario]]
 == References ==
 <references/>
@@ Line 30: / Line 29: @@
 </StructureSection>
 [[Category: Bos taurus]]
-[[Category: Buffalo rat]]
+[[Category: Gallus gallus]]
-[[Category: Chick]]
 [[Category: Large Structures]]
-[[Category: Akhmanova, A]]
+[[Category: Rattus norvegicus]]
-[[Category: Bargsten, K]]
+[[Category: Akhmanova A]]
-[[Category: Cox, D]]
+[[Category: Band Horwitz S]]
-[[Category: Custar, D W]]
+[[Category: Bargsten K]]
-[[Category: Doodhi, H]]
+[[Category: Cox D]]
-[[Category: Grigoriev, I]]
+[[Category: Custar DW]]
-[[Category: Hilbert, M]]
+[[Category: Doodhi H]]
-[[Category: Horwitz, S Band]]
+[[Category: Grigoriev I]]
-[[Category: Hua, S]]
+[[Category: Hilbert M]]
-[[Category: Jiang, K]]
+[[Category: Hua S]]
-[[Category: Kapitein, L C]]
+[[Category: Jiang K]]
-[[Category: Katrukha, E A]]
+[[Category: Kapitein LC]]
-[[Category: Prota, A E]]
+[[Category: Katrukha EA]]
-[[Category: Rodriguez-Garcia, R]]
+[[Category: Prota AE]]
-[[Category: Steinmetz, M O]]
+[[Category: Rodriguez-Garcia R]]
-[[Category: Xiao, H]]
+[[Category: Steinmetz MO]]
-[[Category: Yang, C P.H]]
+[[Category: Xiao H]]
-[[Category: Cell cycle]]
+[[Category: Yang C-PH]]
-[[Category: Cytoskeleton]]
-[[Category: Microtubule]]
-[[Category: Tubulin fold]]

5jh7

From Proteopedia

Current revision

Tubulin-Eribulin complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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