| Structural highlights
Function
VASH2_MOUSE Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146868). Acts as an activator of angiogenesis: expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis (PubMed:19204325).[1] [2]
Publication Abstract from PubMed
The C-terminus of alpha-tubulin undergoes a detyrosination/tyrosination cycle and dysregulation of this cycle is associated with cancer and other diseases. The molecular mechanisms of tubulin tyrosination are well studied, however it has remained unknown how tyrosine is cleaved from the tubulin tail. Here, we report the crystal structure of the long-sought detyrosination enzyme, the VASH2/SVBP heterodimer at 2.2 A resolution and the structure of the tail/VASH2/SVBP complex at 2.5 A resolution. VASH2 possesses a non-canonical Cys-His-Ser catalytic architecture for tyrosine cleavage. The dynamics of the alpha1- and alpha2- helices of VASH2 are related to the insolubility of VASH2. SVBP plays a chaperone-like role by extensively interacting with VASH2 and stabilizing these dynamic helices. A positively charged groove around the catalytic pocket and the alpha1- and alpha2- helices of VASH2 targets the tubulin tail for detyrosination. We provide insights into the mechanisms underlying the cycle of tubulin tyrosine cleavage and religation.
Structural basis of tubulin detyrosination by VASH2/SVBP heterodimer.,Zhou C, Yan L, Zhang WH, Liu Z Nat Commun. 2019 Jul 19;10(1):3212. doi: 10.1038/s41467-019-11277-8. PMID:31324789[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Aillaud C, Bosc C, Peris L, Bosson A, Heemeryck P, Van Dijk J, Le Friec J, Boulan B, Vossier F, Sanman LE, Syed S, Amara N, Coute Y, Lafanechere L, Denarier E, Delphin C, Pelletier L, Humbert S, Bogyo M, Andrieux A, Rogowski K, Moutin MJ. Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation. Science. 2017 Dec 15;358(6369):1448-1453. doi: 10.1126/science.aao4165. Epub 2017, Nov 16. PMID:29146868 doi:http://dx.doi.org/10.1126/science.aao4165
- ↑ Zhou C, Yan L, Zhang WH, Liu Z. Structural basis of tubulin detyrosination by VASH2/SVBP heterodimer. Nat Commun. 2019 Jul 19;10(1):3212. doi: 10.1038/s41467-019-11277-8. PMID:31324789 doi:http://dx.doi.org/10.1038/s41467-019-11277-8
|
