biostudies-literatureUnknown72(7)Protze JClostridium perfringens enterotoxin (CPE) binds to distinct claudins (Clds), which regulate paracellular barrier functions in endo- and epithelia. The C-terminal domain (cCPE) has the potential for selective claudin modulation, since it only binds to a subset of claudins, e.g., Cld3 and Cld4 (cCPE receptors). Cld5 (non-CPE receptor) is a main constituent in tight junctions (TJ) of the blood-brain barrier. We aimed to reveal claudin recognition mechanisms of cCPE and to create a basis for a Cld5-binder. By utilizing structure-based interaction models, mutagenesis and assays of cCPE-binding to the TJ-free cell line HEK293, transfected with human Cld1 and murine Cld5, we showed how cCPE-binding to Cld1 and Cld5 is prevented by two residues in extracellular loop 2 of Cld1 (Asn(150) and Thr(153Cellular and molecular life sciences : CMLS1417-32https://www.ebi.ac.uk/biostudies/studies/S-EPMC11113963biostudies-literatureDirected structural modification of Clostridium perfringens enterotoxin to enhance binding to claudin-5.PMC11113963Blecharz KGEichner MProtze JPiontek JVajkoczy PPiontek ARossa JDinter SKrause GfalseDirected structural modification of Clostridium perfringens enterotoxin to enhance binding to claudin-5.Clostridium perfringens enterotoxin (CPE) binds to distinct claudins (Clds), which regulate paracellular barrier functions in endo- and epithelia. The C-terminal domain (cCPE) has the potential for selective claudin modulation, since it only binds to a subset of claudins, e.g., Cld3 and Cld4 (cCPE receptors). Cld5 (non-CPE receptor) is a main constituent in tight junctions (TJ) of the blood-brain barrier. We aimed to reveal claudin recognition mechanisms of cCPE and to create a basis for a Cld5-binder. By utilizing structure-based interaction models, mutagenesis and assays of cCPE-binding to the TJ-free cell line HEK293, transfected with human Cld1 and murine Cld5, we showed how cCPE-binding to Cld1 and Cld5 is prevented by two residues in extracellular loop 2 of Cld1 (Asn(150) and Thr(1532015-01-01T00:00:00Z2015 Apr2026-06-02T06:14:47.372Z2026-04-15T03:14:52.562ZS-EPMC111139632534222110.1007/s00018-014-1761-6