| Structural highlights
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
Vasohibins are tubulin tyrosine carboxypeptidases that are important in neuron physiology. We examined the crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal alpha-tubulin peptide. In combination with functional data, we propose that SVBP acts as an activator of vasohibins. An extended groove and a distinctive surface residue patch of vasohibins define the specific determinants for recognizing and cleaving the C-terminal tyrosine of alpha-tubulin and for binding microtubules, respectively. The vasohibin-SVBP interaction and the ability of the enzyme complex to associate with microtubules regulate axon specification of neurons. Our results define the structural basis of tubulin detyrosination by vasohibins and show the relevance of this process for neuronal development. Our findings offer a unique platform for developing drugs against human conditions with abnormal tubulin tyrosination levels, such as cancer, heart defects and possibly brain disorders.
Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme complex.,Wang N, Bosc C, Ryul Choi S, Boulan B, Peris L, Olieric N, Bao H, Krichen F, Chen L, Andrieux A, Olieric V, Moutin MJ, Steinmetz MO, Huang H Nat Struct Mol Biol. 2019 Jul;26(7):571-582. doi: 10.1038/s41594-019-0241-y. Epub, 2019 Jun 24. PMID:31235911[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Wang N, Bosc C, Ryul Choi S, Boulan B, Peris L, Olieric N, Bao H, Krichen F, Chen L, Andrieux A, Olieric V, Moutin MJ, Steinmetz MO, Huang H. Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme complex. Nat Struct Mol Biol. 2019 Jul;26(7):571-582. doi: 10.1038/s41594-019-0241-y. Epub, 2019 Jun 24. PMID:31235911 doi:http://dx.doi.org/10.1038/s41594-019-0241-y
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