2. Academic Validation
  3. Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme complex

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.
Na Wang 1,  Christophe Bosc 2,  Sung Ryul Choi 3,  Benoit Boulan 2,  Leticia Peris 2,  Natacha Olieric 3,  Hongyu Bao 1,  Fatma Krichen 2,  Liu Chen 1,  Annie Andrieux 2,  Vincent Olieric 4,  Marie-Jo Moutin 5,  Michel O Steinmetz 6 7,  Hongda Huang 8
Affiliations

Affiliations

  • 1 Department of Biology, Southern University of Science and Technology, Shenzhen, China.
  • 2 Grenoble Institut Neurosciences, University Grenoble Alpes, Inserm, U1216, CNRS, CEA, Grenoble, France, Grenoble, France.
  • 3 Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen PSI, Switzerland.
  • 4 Laboratory for Macromolecules and Bioimaging, Photon Science Division, Paul Scherrer Institut, Villigen PSI, Switzerland.
  • 5 Grenoble Institut Neurosciences, University Grenoble Alpes, Inserm, U1216, CNRS, CEA, Grenoble, France, Grenoble, France. [email protected].
  • 6 Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen PSI, Switzerland. [email protected].
  • 7 University of Basel, Biozentrum, Basel, Switzerland. [email protected].
  • 8 Department of Biology, Southern University of Science and Technology, Shenzhen, China. [email protected].
PMID: 31235911 DOI: 10.1038/s41594-019-0241-y
Abstract

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 α-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 α-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.

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