9CMI

Cryo-EM structure of human claudin-4 complex with Clostridium perfringens enterotoxin, sFab COP-1, and Nanobody

9CMI の概要

• エントリーDOI: 10.2210/pdb9cmi/pdb
• 関連するPDBエントリー: 9CMH
• EMDBエントリー: 45748 45749
• 分子名称: Claudin-4, Heat-labile enterotoxin B chain, COP-1 sFab Heavy Chain, ... (7 entities in total)
• 機能のキーワード: claudin, fab, enterotoxin, nanobody, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 123274.90

構造登録者

Vecchio, A.J. (登録日: 2024-07-15, 公開日: 2024-08-07, 最終更新日: 2024-11-27)

主引用文献

Rathnayake, S.S.,Erramilli, S.K.,Kossiakoff, A.A.,Vecchio, A.J.
Cryo-EM structures of Clostridium perfringens enterotoxin bound to its human receptor, claudin-4.
Structure, 32:1936-, 2024

PubMed Abstract: Clostridium perfringens enterotoxin (CpE) causes prevalent and deadly gastrointestinal disorders. CpE binds to receptors called claudins on the apical surfaces of small intestinal epithelium. Claudins normally regulate paracellular transport but are hijacked from doing so by CpE and are instead led to form claudin/CpE complexes. Claudin/CpE complexes are the building blocks of oligomeric β-barrel pores that penetrate the plasma membrane and induce gut cytotoxicity. Here, we present the structures of CpE in complex with its native claudin receptor in humans, claudin-4, using cryogenic electron microscopy. The structures reveal the architecture of the claudin/CpE complex, the residues used in binding, the orientation of CpE relative to the membrane, and CpE-induced changes to claudin-4. Further, structures and modeling allude to the biophysical procession from claudin/CpE complexes to cytotoxic β-barrel pores during pathogenesis. In full, this work proposes a model of claudin/CpE assembly and provides strategies to obstruct its formation to treat CpE diseases.

PubMed: 39383874
DOI: 10.1016/j.str.2024.09.015

実験手法

ELECTRON MICROSCOPY (2.83 Å)