Cryo-EM structure of VASH1-SVBP bound to microtubules
- University of Texas Southwestern Medical Center, United States
- Westlake University, China
Abstract
The dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The carboxypeptidases vasohibins 1 and 2 (VASH1 and VASH2), in complex with the small vasohibin-binding protein (SVBP), mediate α-tubulin detyrosination. These enzymes detyrosinate microtubules more efficiently than soluble αβ-tubulin heterodimers. The structural basis for this substrate preference is not understood. Using cryo-electron microscopy (cryo-EM), we have determined the structure of human VASH1-SVBP bound to microtubules. The acidic C-terminal tail of α-tubulin binds to a positively charged groove near the active site of VASH1. VASH1 forms multiple additional contacts with the globular domain of α-tubulin, including contacts with a second α-tubulin in an adjacent protofilament. Simultaneous engagement of two protofilaments by VASH1 can only occur within the microtubule lattice, but not with free αβ heterodimers. These lattice-specific interactions enable preferential detyrosination of microtubules by VASH1.
Data availability
Coordinates and EM density maps have been deposited into the Protein Data Bank under the accession code 6WSL and EMD-21893, respectively.
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Cryo-EM structure of VASH1-SVBP bound to microtubulesProtein Data Bank, 6WSL.
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Cryo-EM structure of VASH1-SVBP bound to microtubulesProtein Data Bank, EMD-21893.
Article and author information
Author details
Funding
National Institutes of Health (GM107415)
- Xuelian Luo
National Institutes of Health (GM098543)
- Luke M Rice
Cancer Prevention and Research Institute of Texas (RP160255)
- Xuelian Luo
Cancer Prevention and Research Institute of Texas (RP160667-P2)
- Hongtao Yu
Welch Foundation (I-1932)
- Xuelian Luo
Welch Foundation (I-1908)
- Luke M Rice
Welch Foundation (I-1441)
- Hongtao Yu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cryo-EM structure of VASH1-SVBP bound to microtubules
eLife 9:e58157.
https://doi.org/10.7554/eLife.58157
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