6j7b

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of VASH1-SVBP in complex with epoY

Structural highlights

6j7b is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.618Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

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

References

↑ Watanabe K, Hasegawa Y, Yamashita H, Shimizu K, Ding Y, Abe M, Ohta H, Imagawa K, Hojo K, Maki H, Sonoda H, Sato Y. Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J Clin Invest. 2004 Oct;114(7):898-907. doi: 10.1172/JCI21152. PMID:15467828 doi:http://dx.doi.org/10.1172/JCI21152
↑ Sonoda H, Ohta H, Watanabe K, Yamashita H, Kimura H, Sato Y. Multiple processing forms and their biological activities of a novel angiogenesis inhibitor vasohibin. Biochem Biophys Res Commun. 2006 Apr 7;342(2):640-6. Epub 2006 Feb 13. PMID:16488400 doi:http://dx.doi.org/S0006-291X(06)00167-7
↑ Yamashita H, Abe M, Watanabe K, Shimizu K, Moriya T, Sato A, Satomi S, Ohta H, Sonoda H, Sato Y. Vasohibin prevents arterial neointimal formation through angiogenesis inhibition. Biochem Biophys Res Commun. 2006 Jul 7;345(3):919-25. doi:, 10.1016/j.bbrc.2006.04.176. Epub 2006 May 8. PMID:16707096 doi:http://dx.doi.org/10.1016/j.bbrc.2006.04.176
↑ Kimura H, Miyashita H, Suzuki Y, Kobayashi M, Watanabe K, Sonoda H, Ohta H, Fujiwara T, Shimosegawa T, Sato Y. Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis. Blood. 2009 May 7;113(19):4810-8. doi: 10.1182/blood-2008-07-170316. Epub 2009, Feb 9. PMID:19204325 doi:http://dx.doi.org/10.1182/blood-2008-07-170316
↑ Nieuwenhuis J, Adamopoulos A, Bleijerveld OB, Mazouzi A, Stickel E, Celie P, Altelaar M, Knipscheer P, Perrakis A, Blomen VA, Brummelkamp TR. Vasohibins encode tubulin detyrosinating activity. Science. 2017 Dec 15;358(6369):1453-1456. doi: 10.1126/science.aao5676. Epub 2017, Nov 16. PMID:29146869 doi:http://dx.doi.org/10.1126/science.aao5676
↑ Liao S, Rajendraprasad G, Wang N, Eibes S, Gao J, Yu H, Wu G, Tu X, Huang H, Barisic M, Xu C. Molecular basis of vasohibins-mediated detyrosination and its impact on spindle function and mitosis. Cell Res. 2019 Jun 6. pii: 10.1038/s41422-019-0187-y. doi:, 10.1038/s41422-019-0187-y. PMID:31171830 doi:http://dx.doi.org/10.1038/s41422-019-0187-y

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/6j7b"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[6j7b]] 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=6J7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J7B 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]] 1.618&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BJL:N-[(3R)-4-ethoxy-3-hydroxy-4-oxobutanoyl]-L-tyrosine'>BJL</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BJL:(2~{S})-2-[[(3~{R})-4-ethoxy-3-oxidanyl-4-oxidanylidene-butanoyl]amino]-3-(4-hydroxyphenyl)propanoic+acid'>BJL</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=6j7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j7b OCA], [https://pdbe.org/6j7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j7b RCSB], [https://www.ebi.ac.uk/pdbsum/6j7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j7b ProSAT]</span></td></tr>
 </table>

6j7b

From Proteopedia

Current revision

Crystal structure of VASH1-SVBP in complex with epoY

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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