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Updated: Jan 22, 2026

Author Spotlight: Purifying High-Quality Tubulin to Study Protein Dynamics and Therapeutic Applications
Published on: October 11, 2024
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.
Abstract:
The C-terminus of α-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 Å resolution and the structure of the tail/VASH2/SVBP complex at 2.5 Å resolution. VASH2 possesses a non-canonical Cys-His-Ser catalytic architecture for tyrosine cleavage. The dynamics of the α1- and α2- 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 α1- and α2- helices of VASH2 targets the tubulin tail for detyrosination. We provide insights into the mechanisms underlying the cycle of tubulin tyrosine cleavage and religation.
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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