7ZCW

Cryo-EM structure of GMPCPP-microtubules in complex with VASH2-SVBP

Summary for 7ZCW

• Entry DOI: 10.2210/pdb7zcw/pdb
• EMDB information: 14634
• Descriptor: Tubulin alpha-1B chain, Tubulin beta-2B chain, Tubulinyl-Tyr carboxypeptidase 2, ... (7 entities in total)
• Functional Keywords: microtubule, enzyme, complex, detyrosination, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 352585.91

Authors

Choi, S.R.,Blum, T.,Steinmetz, M.O. (deposition date: 2022-03-29, release date: 2022-12-14, Last modification date: 2024-07-24)

Primary citation

Ramirez-Rios, S.,Choi, S.R.,Sanyal, C.,Blum, T.B.,Bosc, C.,Krichen, F.,Denarier, E.,Soleilhac, J.M.,Blot, B.,Janke, C.,Stoppin-Mellet, V.,Magiera, M.M.,Arnal, I.,Steinmetz, M.O.,Moutin, M.J.
VASH1-SVBP and VASH2-SVBP generate different detyrosination profiles on microtubules.
J.Cell Biol., 222:-, 2023

PubMed Abstract: The detyrosination/tyrosination cycle of α-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.

PubMed: 36512346
DOI: 10.1083/jcb.202205096

Experimental method

ELECTRON MICROSCOPY (3.6 Å)