| RRC ID |
85372
|
| Author |
Yoshida T, Monma C, Ninomiya Y, Takiguchi S, Fujita S, Uchida Y, Sakoda N, Karginov VA, Kishikawa JI, Yamada T, Kawano R, Tsuge H.
|
| Title |
Serine clamp of Clostridium perfringens binary toxin BECb (CPILEb)-pore confers cytotoxicity and enterotoxicity.
|
| Journal |
Commun Biol
|
| Abstract |
BEC (CPILE) is a virulence factor of the pathogen, Clostridium perfringens, which has caused foodborne outbreaks in Japan. BEC is a binary toxin that comprises the enzymatic A-component (BECa) and the B-component (BECb); the latter forms a membrane pore to translocate the A-component into target cells. Although BEC differs from other binary toxins in that the B-component alone shows enterotoxic activity, the reason for this remains unclear. We focus on the narrowest region of BECb-pore formed by not phenylalanine residues conserved in other binary toxins including iota toxin B-component (Ib) but serine residues. Comparisons between BECb and BECb (S405F) where the serine residue forming the narrowest region is substituted to the phenylalanine residue reveal that the serine residue is responsible for both cytotoxicity and enterotoxic activity. Though attempts to prepare the BECb-pore were unsuccessful, we reveal the cryo-EM structure of Ib (F454S) where the phenylalanine residue forming the narrowest region is substituted to the serine residue as a surrogate of BECb. Furthermore, Ib (F454S) increases current conductance to nine times that of Ib due to the larger pore diameter and the hydrophilic nature. These results suggest that BECb functions as a pore-forming toxin and as a translocation channel for BECa.
|
| Volume |
8(1)
|
| Pages |
1102
|
| Published |
2025-7-25
|
| DOI |
10.1038/s42003-025-08519-5
|
| PII |
10.1038/s42003-025-08519-5
|
| PMID |
40715636
|
| PMC |
PMC12297211
|
| MeSH |
Animals
Bacterial Proteins* / chemistry
Bacterial Proteins* / genetics
Bacterial Proteins* / metabolism
Bacterial Toxins* / chemistry
Bacterial Toxins* / genetics
Bacterial Toxins* / metabolism
Bacterial Toxins* / toxicity
Clostridium perfringens* / genetics
Clostridium perfringens* / metabolism
Clostridium perfringens* / pathogenicity
Cryoelectron Microscopy
Humans
Serine* / chemistry
Serine* / metabolism
|
| IF |
4.165
|
| Resource |
| Human and Animal Cells |
A431(RCB0202)
L929(RCB1422)
MDCK(RCB0995) |
