8u5d

Crystal Structure of C-terminal domain of Clostridium perfringens Enterotoxin in Space Group P 41 21 2

spinqualitylabelsall models 8u5d, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8u5d is a 2 chain structure with sequence from Clostridium perfringens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: ACT, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ELTB_CLOPF This enterotoxin is responsible for many cases of a mild type of food poisoning. Publication Abstract from PubMed Clostridium perfringens enterotoxin (CpE) is a beta-pore forming toxin that disrupts gastrointestinal homeostasis in mammals by binding membrane protein receptors called claudins. Although structures of CpE fragments bound to claudins have been determined, the mechanisms that trigger CpE activation and oligomerization that lead to the formation of cytotoxic beta-pores remain undetermined. Proteolysis of CpE in the gut by trypsin has been shown to play a role in this and subsequent cytotoxicity processes. Here, we report solution structures of full-length and trypsinized CpE using small-angle X-ray scattering (SAXS) and crystal structures of trypsinized CpE and its C-terminal claudin-binding domain (cCpE) using X-ray crystallography. Mass spectrometry and SAXS uncover that removal of the CpE N-terminus by trypsin alters the CpE structure to expose areas that are normally unexposed. Crystal structures of trypsinized CpE and cCpE reveal unique dimer interfaces that could serve as oligomerization sites. Moreover, comparisons of these structures to existing ones predict the functional implications of oligomerization in the contexts of cell receptor binding and beta-pore formation. This study sheds light on trypsin's role in altering CpE structure to activate its function via inducing oligomerization on its path toward cytotoxic beta-pore formation. Its findings can incite new approaches to inhibit CpE-based cytotoxicity with oligomer-disrupting therapeutics. Structural Basis of Clostridium perfringens Enterotoxin Activation and Oligomerization by Trypsin.,Ogbu CP, Kapoor S, Vecchio AJ Toxins (Basel). 2023 Oct 31;15(11):637. doi: 10.3390/toxins15110637. PMID:37999500 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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