6J91

Structure of a hypothetical protease

Summary for 6J91

• Entry DOI: 10.2210/pdb6j91/pdb
• Descriptor: Small vasohibin-binding protein, Tubulinyl-Tyr carboxypeptidase 1 (2 entities in total)
• Functional Keywords: protease, complex, peptide binding protein, peptide binding protein-hydrolase complex, peptide binding protein/hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 36005.88

Authors

Liao, S.,Gao, J.,Xu, C. (deposition date: 2019-01-21, release date: 2019-06-19, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.5 Å)