6jze

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Crystal structure of VASH2-SVBP complex with the magic triangle I3C

Structural highlights

6jze is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:I3C
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[1] [2] [3]

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[4]

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

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Citations
5 reviews cite this structure
The tubulin code and its role in controlling microtubule properties and functions.
Janke et al. (2020)
4 more
8 other articles
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See Also

References

  1. ↑ Suzuki Y, Kobayashi M, Miyashita H, Ohta H, Sonoda H, Sato Y. Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion. J Cell Sci. 2010 Sep 15;123(Pt 18):3094-101. doi: 10.1242/jcs.067538. Epub 2010, Aug 24. PMID:20736312 doi:http://dx.doi.org/10.1242/jcs.067538
  2. ↑ Kadonosono T, Yimchuen W, Tsubaki T, Shiozawa T, Suzuki Y, Kuchimaru T, Sato Y, Kizaka-Kondoh S. Domain architecture of vasohibins required for their chaperone-dependent unconventional extracellular release. Protein Sci. 2017 Mar;26(3):452-463. doi: 10.1002/pro.3089. Epub 2017 Feb 11. PMID:27879017 doi:http://dx.doi.org/10.1002/pro.3089
  3. ↑ 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
  4. ↑ 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

Contents


PDB ID 6jze

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