Anthrax Lethal Factor: Difference between revisions
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Anthrax Toxin is considered an AB toxin, with two A domains (EF and LF) and one B domain (PA). <ref>Brenda A. Wilson, Abigail A. Salyers, Dixie D. Whitt, and Malcolm E. Winkler. Third Edition. Bacterial Pathogenesis A Molecular Approach</ref> On their own, these three domains are nontoxic, but any combination involving PA with EF and/or LF is what causes the physiological effects. <ref>Kenneth Todar, PhD. (2008). http://textbookofbacteriology.net/Anthrax_3.html</ref> Initially PA is a 83kDa protein which binds to the host Anthrax toxin Receptor (ATR). Upon binding, PA is cleaved into two fragments by a furin proteases to become a 63 kDa protein bound to the ATR. Cleavage of PA allows self associate to occur which forms a ring shaped heptamer know as the pore precursor (prepore). The prepore is now able to bind up to three molecules of EF and/or LF, leading to endocytosis of the complex. In the endosome, the prepore converts to a transmembrane pore, allowing translocation of EF and LF to the cytosol through a mechanism that is not will understood. EF and LF are now able to carry out their enzymatic activity on the host cell. <ref name=Collier>PMID: 14570563</ref> | Anthrax Toxin is considered an AB toxin, with two A domains (EF and LF) and one B domain (PA). <ref>Brenda A. Wilson, Abigail A. Salyers, Dixie D. Whitt, and Malcolm E. Winkler. Third Edition. Bacterial Pathogenesis A Molecular Approach</ref> On their own, these three domains are nontoxic, but any combination involving PA with EF and/or LF is what causes the physiological effects. <ref>Kenneth Todar, PhD. (2008). http://textbookofbacteriology.net/Anthrax_3.html</ref> Initially PA is a 83kDa protein which binds to the host Anthrax toxin Receptor (ATR). Upon binding, PA is cleaved into two fragments by a furin proteases to become a 63 kDa protein bound to the ATR. Cleavage of PA allows self associate to occur which forms a ring shaped heptamer know as the pore precursor (prepore). The prepore is now able to bind up to three molecules of EF and/or LF, leading to endocytosis of the complex. In the endosome, the prepore converts to a transmembrane pore, allowing translocation of EF and LF to the cytosol through a mechanism that is not will understood. EF and LF are now able to carry out their enzymatic activity on the host cell. <ref name=Collier>PMID: 14570563</ref> | ||
EF is a calmodulin and calcium dependent adenylate cyclase which causes the edema associated with the disease. <ref name=Collier>PMID: 14570563</ref> | EF is a calmodulin and calcium dependent adenylate cyclase which causes the edema associated with the disease. <ref name=Collier>PMID: 14570563</ref> <ref name=Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC>PMID: 11700563</ref> | ||
LF is a Zinc dependent protease that cleaves certain MAP kinase kinases (MAPKK)leading to the disruption of many cellular signalling pathways, which eventually leads to cell death. <ref name=Collier>PMID: 14570563</ref> | LF is a Zinc dependent protease that cleaves certain MAP kinase kinases (MAPKK)leading to the disruption of many cellular signalling pathways, which eventually leads to cell death. <ref name=Collier>PMID: 14570563</ref> <ref name=Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC>PMID: 11700563</ref> | ||
This is a list of the possible combinations that can occur with Anthrax Toxin: <ref>Kenneth Todar, PhD. (2008). http://textbookofbacteriology.net/Anthrax_3.html</ref> | |||
PA+LF Leads to lethal activity | |||
EF+PA Leads to edema | |||
EF+LF Non-toxic | |||
PA+LF+EF Leads to lethal activity and edema | |||
==Human Interaction== | ==Human Interaction== | ||