7zcw

Publication Abstract from PubMed

The detyrosination/tyrosination cycle of alpha-tubulin is critical for proper cell functioning. VASH1-SVBP and VASH2-SVBP are ubiquitous enzymes involved in microtubule detyrosination, whose mode of action is little known. Here, we show in reconstituted systems and cells that VASH1-SVBP and VASH2-SVBP drive the global and local detyrosination of microtubules, respectively. We solved the cryo-electron microscopy structure of VASH2-SVBP bound to microtubules, revealing a different microtubule-binding configuration of its central catalytic region compared to VASH1-SVBP. We 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 region is critical for microtubule detachment and diffusion of VASH-SVBP enzymes on lattices. Our results suggest a mechanism by which VASH1-SVBP and VASH2-SVBP could generate distinct microtubule subpopulations and confined areas of detyrosinated lattices to drive various microtubule-based cellular functions.

VASH1-SVBP and VASH2-SVBP generate different detyrosination profiles on microtubules.,Ramirez-Rios S, Choi SR, Sanyal C, Blum TB, Bosc C, Krichen F, Denarier E, Soleilhac JM, Blot B, Janke C, Stoppin-Mellet V, Magiera MM, Arnal I, Steinmetz MO, Moutin MJ J Cell Biol. 2023 Feb 6;222(2):e202205096. doi: 10.1083/jcb.202205096. Epub 2022 , Dec 13. PMID:36512346^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.