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-Structure paper
| タイトル | Cryo-EM structures of Clostridium perfringens enterotoxin bound to its human receptor, claudin-4. |
|---|---|
| ジャーナル・号・ページ | Structure, Vol. 32, Issue 11, Page 1936-11951.e5, Year 2024 |
| 掲載日 | 2024年11月7日 |
著者 | Sewwandi S Rathnayake / Satchal K Erramilli / Anthony A Kossiakoff / Alex J Vecchio / ![]() |
| PubMed 要旨 | Clostridium perfringens enterotoxin (CpE) causes prevalent and deadly gastrointestinal disorders. CpE binds to receptors called claudins on the apical surfaces of small intestinal epithelium. ...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. |
リンク | Structure / PubMed:39383874 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.83 - 4.0 Å |
| 構造データ | EMDB-45748, PDB-9cmh: EMDB-45749, PDB-9cmi: |
| 化合物 | ![]() ChemComp-AV0: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / claudin / enterotoxin / Fab / nanobody |
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homo sapiens (ヒト)
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