6j7b
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of VASH1-SVBP in complex with epoY== | |
| + | <StructureSection load='6j7b' size='340' side='right'caption='[[6j7b]], [[Resolution|resolution]] 1.62Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6j7b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J7B FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BJL:N-[(3R)-4-ethoxy-3-hydroxy-4-oxobutanoyl]-L-tyrosine'>BJL</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tubulinyl-Tyr_carboxypeptidase Tubulinyl-Tyr carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.17 3.4.17.17] </span></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=6j7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j7b OCA], [http://pdbe.org/6j7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j7b RCSB], [http://www.ebi.ac.uk/pdbsum/6j7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j7b ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/VASH1_HUMAN VASH1_HUMAN]] Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146869). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:15467828, PubMed:16488400, PubMed:16707096, PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400, PubMed:16707096).<ref>PMID:15467828</ref> <ref>PMID:16488400</ref> <ref>PMID:16707096</ref> <ref>PMID:19204325</ref> <ref>PMID:29146869</ref> [[http://www.uniprot.org/uniprot/SVBP_HUMAN SVBP_HUMAN]] Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin (PubMed:29146869). Also required to enhance the solubility and secretion of VASH1 and VASH2 (PubMed:20736312, PubMed:27879017).<ref>PMID:20736312</ref> <ref>PMID:27879017</ref> <ref>PMID:29146869</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | alpha-Tubulin detyrosination, largely catalyzed by vasohibins, is involved in many microtubule (MT)-related cellular events. In this study, we identified a core heterodimeric complex of human small vasohibin-binding protein (SVBP) and vasohibin 1 (VASH1) (hereafter denoted as SVBP-VASH1) that catalyzes the detyrosination of a peptide derived from C-terminus of alpha-tubulin. We further solved the crystal structures of the SVBP-VASH1 heterodimer alone and in complex with either an inhibitor or a mutant substrate peptide. Our structural research, complemented by biochemical and mutagenesis experiments, resulted in identification of the key residues for VASH1 binding to SVBP and alpha-tubulin substrate. Our in vivo experiments reveal that MT detyrosination in general, as well as the interactions between SVBP, VASH1, and alpha-tubulin, are critical for spindle function and accurate chromosome segregation during mitosis. Furthermore, we found that the phenotypes caused by the depletion of vasohibins were largely rescued upon co-depletion of kinesin13/MCAK, suggesting the coordination between the MT depolymerase and MT detyrosination during mitosis. Thus our work not only provides structural insights into the molecular mechanism of alpha-tubulin detyrosination catalyzed by SVBP-bound vasohibins, but also uncovers the key role of vasohibins-mediated MT detyrosination in spindle morphology and chromosome segregation during mitosis. | ||
| - | + | Molecular basis of vasohibins-mediated detyrosination and its impact on spindle function and mitosis.,Liao S, Rajendraprasad G, Wang N, Eibes S, Gao J, Yu H, Wu G, Tu X, Huang H, Barisic M, Xu C Cell Res. 2019 Jun 6. pii: 10.1038/s41422-019-0187-y. doi:, 10.1038/s41422-019-0187-y. PMID:31171830<ref>PMID:31171830</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6j7b" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Tubulinyl-Tyr carboxypeptidase]] | ||
| + | [[Category: Bao, H]] | ||
| + | [[Category: Huang, H]] | ||
| + | [[Category: Wang, N]] | ||
| + | [[Category: Wu, B]] | ||
| + | [[Category: Carboxypeptidase]] | ||
| + | [[Category: Epoy]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Microtubule]] | ||
| + | [[Category: Tubulin]] | ||
Revision as of 05:56, 19 June 2019
Crystal structure of VASH1-SVBP in complex with epoY
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Categories: Large Structures | Tubulinyl-Tyr carboxypeptidase | Bao, H | Huang, H | Wang, N | Wu, B | Carboxypeptidase | Epoy | Hydrolase | Inhibitor | Microtubule | Tubulin
