Cryo-EM structure of VASH1-SVBP bound to microtubules

Elife. 2020 Aug 10:9:e58157. doi: 10.7554/eLife.58157.


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.

Keywords: E. coli; cryo-electron microscopy; detyrosination; microtubule; molecular biophysics; posttranslational modification; structural biology; vasohibin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry*
  • Carrier Proteins / ultrastructure*
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / ultrastructure*
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • HeLa Cells
  • Humans
  • Microtubules / ultrastructure*
  • Protein Conformation
  • Tubulin / chemistry*
  • Tyrosine / chemistry


  • Carrier Proteins
  • Cell Cycle Proteins
  • SVBP protein, human
  • Tubulin
  • VASH1 protein, human
  • Tyrosine