VASH1-SVBP and VASH2-SVBP generate different detyrosination profiles on microtubules - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2022

VASH1-SVBP and VASH2-SVBP generate different detyrosination profiles on microtubules

Chadni Sanyal
Thorsten Blum
Eric Denarier
Carsten Janke
Maria Magiera
Isabelle Arnal
Michel Steinmetz

Résumé

ABSTRACT The detyrosination/tyrosination cycle of α-tubulin is critical for proper cell functioning. VASH1-SVBP and VASH2-SVBP are ubiquitous enzyme complexes involved in microtubule detyrosination. However, little is known about their mode of action. Here, we show in reconstituted systems and in cells that VASH1-SVBP and VASH2-SVBP drive global and local detyrosination of microtubules, respectively. We solved the cryo-electron microscopy structure of human VASH2-SVBP bound to microtubules, revealing a different microtubule-binding configuration of its central catalytic region compared to VASH1-SVBP. We further show that the divergent mode of detyrosination between the two enzymes is correlated with the microtubule-binding properties of their disordered N- and C-terminal regions. Specifically, the N-terminal region is responsible for a significantly longer residence time of VASH2-SVBP on microtubules compared to VASH1-SVBP. We suggest that this VASH domain is critical for microtubule-detachment and diffusion of VASH-SVBP enzymes on the lattice. Together, our results suggest a mechanism by which these enzymes could generate distinct microtubule subpopulations and confined areas of detyrosinated lattices to drive various microtubule-based cellular functions. SUMMARY VASH1-SVBP and VASH2-SVBP produce global and local detyrosination patterns of microtubule lattices, respectively. These activities rely on the interplay between the N- and C-terminal disordered regions of the enzymes, which determine their differential molecular mechanism of action. GRAPHICAL ABSTRACT Schematic representation of divergent molecular mechanisms of action of VASH-SVBP detyrosination complexes.

Dates et versions

hal-03839931 , version 1 (04-11-2022)

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Sacnicte Ramirez-Rios, Sung Ryul Choi, Chadni Sanyal, Thorsten Blum, Christophe Bosc, et al.. VASH1-SVBP and VASH2-SVBP generate different detyrosination profiles on microtubules. 2022. ⟨hal-03839931⟩
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