9BEI

Cryo-EM structure of synthetic claudin-4 complex with Clostridium perfringens enterotoxin C-terminal domain, sFab COP-2, and Nanobody

これはPDB形式変換不可エントリーです。

9BEI の概要

• エントリーDOI: 10.2210/pdb9bei/pdb
• 関連するPDBエントリー: 7DTM
• EMDBエントリー: 44479
• 分子名称: Claudin-4, Heat-labile enterotoxin B chain, COP-2 Fab Heavy chain, ... (5 entities in total)
• 機能のキーワード: claudin, fab, toxin, membrane protein, membrane protein-immune sysytem complex, membrane protein/immune sysytem
• 由来する生物種: Clostridium perfringens; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 98625.79

構造登録者

Vecchio, A.J. (登録日: 2024-04-15, 公開日: 2024-04-24, 最終更新日: 2024-10-16)

主引用文献

Goverde, C.A.,Pacesa, M.,Goldbach, N.,Dornfeld, L.J.,Balbi, P.E.M.,Georgeon, S.,Rosset, S.,Kapoor, S.,Choudhury, J.,Dauparas, J.,Schellhaas, C.,Kozlov, S.,Baker, D.,Ovchinnikov, S.,Vecchio, A.J.,Correia, B.E.
Computational design of soluble and functional membrane protein analogues.
Nature, 631:449-458, 2024

PubMed Abstract: De novo design of complex protein folds using solely computational means remains a substantial challenge. Here we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, such as those from G-protein-coupled receptors, are not found in the soluble proteome, and we demonstrate that their structural features can be recapitulated in solution. Biophysical analyses demonstrate the high thermal stability of the designs, and experimental structures show remarkable design accuracy. The soluble analogues were functionalized with native structural motifs, as a proof of concept for bringing membrane protein functions to the soluble proteome, potentially enabling new approaches in drug discovery. In summary, we have designed complex protein topologies and enriched them with functionalities from membrane proteins, with high experimental success rates, leading to a de facto expansion of the functional soluble fold space.

PubMed: 38898281
DOI: 10.1038/s41586-024-07601-y

実験手法

ELECTRON MICROSCOPY (4.16 Å)