Structural basis of tubulin detyrosination by VASH2/SVBP heterodimer

Chen Zhou1, Ling Yan1, Wen-Hui Zhang1

  • 1National Key Laboratory of Crop Genetic Improvement, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Nature Communications
|July 21, 2019
PubMed

Insights

Scientists have uncovered the structure of the VASH2/SVBP enzyme complex, revealing its mechanism for detyrosination of alpha-tubulin. This finding sheds light on a critical cycle linked to cancer and disease.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • The C-terminus of alpha-tubulin undergoes a detyrosination/tyrosination cycle.
  • Dysregulation of this cycle is implicated in cancer and other diseases.
  • The mechanisms of tubulin tyrosination are understood, but detyrosination mechanisms remain elusive.

Purpose of the Study:

  • To elucidate the molecular mechanisms of tubulin detyrosination.
  • To determine the structure of the VASH2/SVBP heterodimer and its complex with the tubulin tail.

Main Methods:

  • X-ray crystallography was used to determine the structures.
  • The structures of the VASH2/SVBP heterodimer and the tubulin tail/VASH2/SVBP complex were resolved at 2.2 Å and 2.5 Å resolution, respectively.

Main Results:

  • The crystal structure of the VASH2/SVBP heterodimer and its complex with the tubulin tail were determined.
  • VASH2 exhibits a non-canonical Cys-His-Ser catalytic triad for tyrosine cleavage.
  • SVBP acts as a chaperone, stabilizing dynamic helices in VASH2, and a positively charged groove targets the tubulin tail.

Conclusions:

  • The study reveals the structure of the VASH2/SVBP complex, the enzyme responsible for tubulin detyrosination.
  • Insights into the catalytic mechanism and substrate targeting provide a mechanistic understanding of the tubulin tyrosine cycle.

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