6J4V

Structural basis of tubulin detyrosination by vasohibins-SVBP enzyme complex and functional implications

6J4V の概要

• エントリーDOI: 10.2210/pdb6j4v/pdb
• 分子名称: Tubulinyl-Tyr carboxypeptidase 2, Small vasohibin-binding protein, Tubulin alpha-1B chain, ... (6 entities in total)
• 機能のキーワード: carboxypeptidase, tubulin, microtubule., 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: 40009.88

構造登録者

Wang, N.,Bao, H.,Huang, H. (登録日: 2019-01-10, 公開日: 2019-05-01, 最終更新日: 2024-10-30)

主引用文献

Wang, N.,Bosc, C.,Ryul Choi, S.,Boulan, B.,Peris, L.,Olieric, N.,Bao, H.,Krichen, F.,Chen, L.,Andrieux, A.,Olieric, V.,Moutin, M.J.,Steinmetz, M.O.,Huang, H.
Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme complex.
Nat.Struct.Mol.Biol., 26:571-582, 2019

PubMed Abstract: Vasohibins are tubulin tyrosine carboxypeptidases that are important in neuron physiology. We examined the crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal α-tubulin peptide. In combination with functional data, we propose that SVBP acts as an activator of vasohibins. An extended groove and a distinctive surface residue patch of vasohibins define the specific determinants for recognizing and cleaving the C-terminal tyrosine of α-tubulin and for binding microtubules, respectively. The vasohibin-SVBP interaction and the ability of the enzyme complex to associate with microtubules regulate axon specification of neurons. Our results define the structural basis of tubulin detyrosination by vasohibins and show the relevance of this process for neuronal development. Our findings offer a unique platform for developing drugs against human conditions with abnormal tubulin tyrosination levels, such as cancer, heart defects and possibly brain disorders.

PubMed: 31235911
DOI: 10.1038/s41594-019-0241-y

実験手法

X-RAY DIFFRACTION (2.1 Å)