6J8F

Crystal structure of SVBP-VASH1 with peptide mimic the C-terminal of alpha-tubulin

6J8F の概要

• エントリーDOI: 10.2210/pdb6j8f/pdb
• 分子名称: Small vasohibin-binding protein, Tubulinyl-Tyr carboxypeptidase 1, 8-mer peptide, ... (4 entities in total)
• 機能のキーワード: protease, complex, peptide binding protein, structural genomics, psi-2, protein structure initiative, structural genomics consortium, sgc, peptide binding protein-hydrolase complex, peptide binding protein/hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 33993.26

構造登録者

Liao, S.,Gao, J.,Xu, C.,Structural Genomics Consortium (SGC) (登録日: 2019-01-18, 公開日: 2019-06-19, 最終更新日: 2024-04-03)

主引用文献

Liao, S.,Rajendraprasad, G.,Wang, N.,Eibes, S.,Gao, J.,Yu, H.,Wu, G.,Tu, X.,Huang, H.,Barisic, M.,Xu, C.
Molecular basis of vasohibins-mediated detyrosination and its impact on spindle function and mitosis.
Cell Res., 29:533-547, 2019

PubMed Abstract: α-Tubulin detyrosination, largely catalyzed by vasohibins, is involved in many microtubule (MT)-related cellular events. In this study, we identified a core heterodimeric complex of human small vasohibin-binding protein (SVBP) and vasohibin 1 (VASH1) (hereafter denoted as SVBP-VASH1) that catalyzes the detyrosination of a peptide derived from C-terminus of α-tubulin. We further solved the crystal structures of the SVBP-VASH1 heterodimer alone and in complex with either an inhibitor or a mutant substrate peptide. Our structural research, complemented by biochemical and mutagenesis experiments, resulted in identification of the key residues for VASH1 binding to SVBP and α-tubulin substrate. Our in vivo experiments reveal that MT detyrosination in general, as well as the interactions between SVBP, VASH1, and α-tubulin, are critical for spindle function and accurate chromosome segregation during mitosis. Furthermore, we found that the phenotypes caused by the depletion of vasohibins were largely rescued upon co-depletion of kinesin13/MCAK, suggesting the coordination between the MT depolymerase and MT detyrosination during mitosis. Thus our work not only provides structural insights into the molecular mechanism of α-tubulin detyrosination catalyzed by SVBP-bound vasohibins, but also uncovers the key role of vasohibins-mediated MT detyrosination in spindle morphology and chromosome segregation during mitosis.

PubMed: 31171830
DOI: 10.1038/s41422-019-0187-y

実験手法

X-RAY DIFFRACTION (2.283 Å)