7Z6S

MATCAP bound to a human 14 protofilament microtubule

7Z6S の概要

• エントリーDOI: 10.2210/pdb7z6s/pdb
• 関連するPDBエントリー: 7Z5G 7Z5H
• EMDBエントリー: 14529
• 分子名称: Tubulin alpha-1B chain, Tubulin beta-3 chain, Uncharacterized protein KIAA0895-like, ... (7 entities in total)
• 機能のキーワード: detyrosination, microtubule-binding, zinc-metalloprotease, tyrosine carboxypeptidase, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 313771.27

構造登録者

Bak, J.,Perrakis, A. (登録日: 2022-03-14, 公開日: 2022-05-11, 最終更新日: 2024-10-16)

主引用文献

Landskron, L.,Bak, J.,Adamopoulos, A.,Kaplani, K.,Moraiti, M.,van den Hengel, L.G.,Song, J.Y.,Bleijerveld, O.B.,Nieuwenhuis, J.,Heidebrecht, T.,Henneman, L.,Moutin, M.J.,Barisic, M.,Taraviras, S.,Perrakis, A.,Brummelkamp, T.R.
Posttranslational modification of microtubules by the MATCAP detyrosinase.
Science, 376:eabn6020-eabn6020, 2022

PubMed Abstract: The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of α-tubulin and is implicated in cognitive, cardiac, and mitotic defects. The vasohibin-small vasohibin-binding protein (SVBP) complex underlies much, but not all, detyrosination. We used haploid genetic screens to identify an unannotated protein, microtubule associated tyrosine carboxypeptidase (MATCAP), as a remaining detyrosinating enzyme. X-ray crystallography and cryo-electron microscopy structures established MATCAP's cleaving mechanism, substrate specificity, and microtubule recognition. Paradoxically, whereas abrogation of tyrosine religation is lethal in mice, codeletion of MATCAP and SVBP is not. Although viable, defective detyrosination caused microcephaly, associated with proliferative defects during neurogenesis, and abnormal behavior. Thus, MATCAP is a missing component of the detyrosination-tyrosination cycle, revealing the importance of this modification in brain formation.

PubMed: 35482892
DOI: 10.1126/science.abn6020

実験手法

ELECTRON MICROSCOPY (2.9 Å)