Homologous Superfamily

Anthrax toxin, edema factor, central domain superfamily (IPR037017)

Short name: Anthrax_toxin_edema_cen_sf

Description

Anthrax toxin is a plasmid-encoded toxin complex produced by the Gram-positive, spore-forming bacteria, Bacillus anthracis. The toxin consists of three non-toxic proteins: the protective antigen (PA), the lethal factor (LF) and the edema factor (EF) [PMID: 14570563]. These component proteins self-assemble at the surface of host cell receptors, yielding a series of toxic complexes that can produce shock-like symptoms and death. Anthrax toxin is one of a large group of Bacillus and Clostridium exotoxins referred to as binary toxins, forming independent enzymatic (A moiety) and binding (B moiety) components. The LF and EF proteins are the enzymes (A moiety) that act on cytosolic substrates, while PA is a multi-functional protein (B moiety) that binds to cell surface receptors, mediates the assembly and internalisation of the complexes, and delivers them to the host cell endosome [PMID: 17335404]. Once PA is attached to the host receptor [PMID: 17381430], it must then be cleaved by a host cell surface (furin family) protease before it is able to bind EF and LF. The cleavage of the N terminus of PA enables the C-terminal fragment to self-associate into a ring-shaped heptameric complex (prepore) that can bind LF or EF competitively. The PA-LF/EF complex is then internalised by endocytosis, and delivered to the endosome, where PA forms a pore in the endosomal membrane in order to translocate LF and EF to the cytosol. LF is a Zn-dependent metalloprotease that cleaves and inactivates mitogen-activated protein (MAP) kinases, kills macrophages, and causes death of the host by inhibiting cell proliferation [PMID: 14616089, PMID: 11700563]. EF is a calcium-and calmodulin-dependent adenylyl cyclase that can cause edema (fluid-filled swelling) when associated with PA. EF is not toxic by itself, and is required for the survival of germinated Bacillus spores within macrophages at the early stages of infection. EF dramatically elevates the level of host intracellular cAMP, a ubiquitous messenger that integrates many processes of the cell; increases in cAMP can interfere with host intracellular signalling [PMID: 15131111].

This entry represents a central domain superfamily in the edema factor adenylyl cyclase protein of anthrax toxin, as well as in adenylyl cylcases from other bacterial toxins.

GO terms

Biological Process

GO:0009405 pathogenesis

Molecular Function

GO:0008294 calcium- and calmodulin-responsive adenylate cyclase activity

Cellular Component

GO:0005576 extracellular region

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
GENE3D