Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes
Adenylate cyclase toxin (ACT) is one of the principal virulence factors secreted by the whooping cough causative bacterium Bordetella pertussis, and it has a critical role in colonization of the respiratory tract and establishment of the disease. ACT targets phagocytes via binding to the CD11b/CD18...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/9/10/295 |
| _version_ | 1798003886868398080 |
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| author | Helena Ostolaza César Martín David González-Bullón Kepa B. Uribe Asier Etxaniz |
| author_facet | Helena Ostolaza César Martín David González-Bullón Kepa B. Uribe Asier Etxaniz |
| author_sort | Helena Ostolaza |
| collection | DOAJ |
| description | Adenylate cyclase toxin (ACT) is one of the principal virulence factors secreted by the whooping cough causative bacterium Bordetella pertussis, and it has a critical role in colonization of the respiratory tract and establishment of the disease. ACT targets phagocytes via binding to the CD11b/CD18 integrin and delivers its N-terminal adenylate cyclase (AC) domain directly to the cell cytosol, where it catalyzes unregulated conversion of cytosolic ATP into cAMP upon activation by binding to cellular calmodulin. High cAMP levels disrupt bactericidal functions of the immune cells, ultimately leading to cell death. In spite of its relevance in the ACT biology, the mechanism by which its ≈400 amino acid-long AC domain is transported through the target plasma membrane, and is released into the target cytosol, remains enigmatic. This article is devoted to refresh our knowledge on the mechanism of AC translocation across biological membranes. Two models, the so-called “two-step model” and the recently-proposed “toroidal pore model”, will be considered. |
| first_indexed | 2024-04-11T12:14:54Z |
| format | Article |
| id | doaj.art-5a2a1c5576ad406d87e214c5679bb9e6 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T12:14:54Z |
| publishDate | 2017-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-5a2a1c5576ad406d87e214c5679bb9e62022-12-22T04:24:20ZengMDPI AGToxins2072-66512017-09-0191029510.3390/toxins9100295toxins9100295Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological MembranesHelena Ostolaza0César Martín1David González-Bullón2Kepa B. Uribe3Asier Etxaniz4Biofisika Insititute (UPV/EHU, CSIC) and Department of Biochemistry and Molecular Biology, University of Basque Country (UPV/EHU), 48080 Bilbao, SpainBiofisika Insititute (UPV/EHU, CSIC) and Department of Biochemistry and Molecular Biology, University of Basque Country (UPV/EHU), 48080 Bilbao, SpainBiofisika Insititute (UPV/EHU, CSIC) and Department of Biochemistry and Molecular Biology, University of Basque Country (UPV/EHU), 48080 Bilbao, SpainBiofisika Insititute (UPV/EHU, CSIC) and Department of Biochemistry and Molecular Biology, University of Basque Country (UPV/EHU), 48080 Bilbao, SpainBiofisika Insititute (UPV/EHU, CSIC) and Department of Biochemistry and Molecular Biology, University of Basque Country (UPV/EHU), 48080 Bilbao, SpainAdenylate cyclase toxin (ACT) is one of the principal virulence factors secreted by the whooping cough causative bacterium Bordetella pertussis, and it has a critical role in colonization of the respiratory tract and establishment of the disease. ACT targets phagocytes via binding to the CD11b/CD18 integrin and delivers its N-terminal adenylate cyclase (AC) domain directly to the cell cytosol, where it catalyzes unregulated conversion of cytosolic ATP into cAMP upon activation by binding to cellular calmodulin. High cAMP levels disrupt bactericidal functions of the immune cells, ultimately leading to cell death. In spite of its relevance in the ACT biology, the mechanism by which its ≈400 amino acid-long AC domain is transported through the target plasma membrane, and is released into the target cytosol, remains enigmatic. This article is devoted to refresh our knowledge on the mechanism of AC translocation across biological membranes. Two models, the so-called “two-step model” and the recently-proposed “toroidal pore model”, will be considered.https://www.mdpi.com/2072-6651/9/10/295Adenylate cyclaseRTX toxinprotein translocationphospholipase activitymodel membranes |
| spellingShingle | Helena Ostolaza César Martín David González-Bullón Kepa B. Uribe Asier Etxaniz Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes Toxins Adenylate cyclase RTX toxin protein translocation phospholipase activity model membranes |
| title | Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes |
| title_full | Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes |
| title_fullStr | Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes |
| title_full_unstemmed | Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes |
| title_short | Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes |
| title_sort | understanding the mechanism of translocation of adenylate cyclase toxin across biological membranes |
| topic | Adenylate cyclase RTX toxin protein translocation phospholipase activity model membranes |
| url | https://www.mdpi.com/2072-6651/9/10/295 |
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