Cryo-EM structure of VASH1-SVBP bound to microtubules.

ABSTRACT: The dynamic tyrosination-detyrosination cycle of ?-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 ?-tubulin detyrosination. These enzymes detyrosinate microtubules more efficiently than soluble ??-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 ?-tubulin binds to a positively charged groove near the active site of VASH1. VASH1 forms multiple additional contacts with the globular domain of ?-tubulin, including contacts with a second ?-tubulin in an adjacent protofilament. Simultaneous engagement of two protofilaments by VASH1 can only occur within the microtubule lattice, but not with free ?? heterodimers. These lattice-specific interactions enable preferential detyrosination of microtubules by VASH1.

SUBMITTER: Li F 

PROVIDER: S-EPMC7449697 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature