Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin
Clostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1–...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-12-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/7/12/4880 |
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| author | Masataka Oda Yutaka Terao Jun Sakurai Masahiro Nagahama |
| author_facet | Masataka Oda Yutaka Terao Jun Sakurai Masahiro Nagahama |
| author_sort | Masataka Oda |
| collection | DOAJ |
| description | Clostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1–250 aa, N-domain), which is the catalytic site, and a C-terminal domain (251–370 aa, C-domain), which is the membrane-binding site. Immunization of mice with the C-domain of alpha-toxin prevents the gas gangrene caused by C. perfringens, whereas immunization with the N-domain has no effect. The central loop domain (55–93 aa), especially H….SW84Y85….G, plays an important role in the interaction with ganglioside GM1a. The toxin binds to lipid rafts in the presence of a GM1a/TrkA complex, and metabolites from phosphatidylcholine to diacylglycerol through the enzymatic activity of alpha-toxin itself. These membrane dynamics leads to the activation of endogenous PLCγ-1 via TrkA. In addition, treatment with alpha-toxin leads to the formation of diacylglycerol at membrane rafts in ganglioside-deficient DonQ cells; this in turn triggers endocytosis and cell death. This article summarizes the current the membrane-binding mechanism of alpha-toxin in detail. |
| first_indexed | 2024-04-13T08:41:37Z |
| format | Article |
| id | doaj.art-ecfb8a83b7874bcaa79e3a3858277268 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-13T08:41:37Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-ecfb8a83b7874bcaa79e3a38582772682022-12-22T02:53:52ZengMDPI AGToxins2072-66512015-12-017125268527510.3390/toxins7124880toxins7124880Membrane-Binding Mechanism of Clostridium perfringens Alpha-ToxinMasataka Oda0Yutaka Terao1Jun Sakurai2Masahiro Nagahama3Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata 951-8514, JapanDivision of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata 951-8514, JapanDepartment of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, JapanDepartment of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, JapanClostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1–250 aa, N-domain), which is the catalytic site, and a C-terminal domain (251–370 aa, C-domain), which is the membrane-binding site. Immunization of mice with the C-domain of alpha-toxin prevents the gas gangrene caused by C. perfringens, whereas immunization with the N-domain has no effect. The central loop domain (55–93 aa), especially H….SW84Y85….G, plays an important role in the interaction with ganglioside GM1a. The toxin binds to lipid rafts in the presence of a GM1a/TrkA complex, and metabolites from phosphatidylcholine to diacylglycerol through the enzymatic activity of alpha-toxin itself. These membrane dynamics leads to the activation of endogenous PLCγ-1 via TrkA. In addition, treatment with alpha-toxin leads to the formation of diacylglycerol at membrane rafts in ganglioside-deficient DonQ cells; this in turn triggers endocytosis and cell death. This article summarizes the current the membrane-binding mechanism of alpha-toxin in detail.http://www.mdpi.com/2072-6651/7/12/4880Clostridium perfringensalpha-toxinC-domaincentral loop domainphospholipidganglioside GM1aTrkAendocytosisvaccine |
| spellingShingle | Masataka Oda Yutaka Terao Jun Sakurai Masahiro Nagahama Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin Toxins Clostridium perfringens alpha-toxin C-domain central loop domain phospholipid ganglioside GM1a TrkA endocytosis vaccine |
| title | Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin |
| title_full | Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin |
| title_fullStr | Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin |
| title_full_unstemmed | Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin |
| title_short | Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin |
| title_sort | membrane binding mechanism of clostridium perfringens alpha toxin |
| topic | Clostridium perfringens alpha-toxin C-domain central loop domain phospholipid ganglioside GM1a TrkA endocytosis vaccine |
| url | http://www.mdpi.com/2072-6651/7/12/4880 |
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