Crystal structure of the tubulin tyrosine carboxypeptidase complex VASH1-SVBP

  • Nat Struct Mol Biol. 2019 Jul;26(7):567-570. doi: 10.1038/s41594-019-0254-6.
Athanassios Adamopoulos  1  2 ,  Lisa Landskron  1  2 ,  Tatjana Heidebrecht  1  2 ,  Foteini Tsakou  1 ,  Onno B Bleijerveld  3 ,  Maarten Altelaar  3  4 ,  Joppe Nieuwenhuis  1  2 ,  Patrick H N Celie  1 ,  Thijn R Brummelkamp  1  2  5  6 ,  Anastassis Perrakis  7  8
Affiliations
  • 1. Division of Biochemistry, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • 2. Oncode Institute, Division of Biochemistry, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • 3. Proteomics Facility, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • 4. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
  • 5. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • 6. Cancer Genomics Center, Amsterdam, the Netherlands.
  • 7. Division of Biochemistry, the Netherlands Cancer Institute, Amsterdam, the Netherlands. [email protected].
  • 8. Oncode Institute, Division of Biochemistry, the Netherlands Cancer Institute, Amsterdam, the Netherlands. [email protected].
PMID: 31270470 DOI: 10.1038/s41594-019-0254-6
Abstract

The cyclic enzymatic removal and ligation of the C-terminal tyrosine of α-tubulin generates heterogeneous microtubules and affects their functions. Here we describe the crystal and solution structure of the tubulin Carboxypeptidase complex between vasohibin (VASH1) and small vasohibin-binding protein (SVBP), which folds in a long helix, which stabilizes the VASH1 catalytic domain. This structure, combined with molecular docking and mutagenesis experiments, reveals which residues are responsible for recognition and cleavage of the tubulin C-terminal tyrosine.