Anthrax Toxin Lethal Factor 抗体

Synonyms: Lethal factor, LF, Anthrax lethal toxin endopeptidase component, lef, pXO1-107, BXA0172, GBAA_pXO1_0172, LEF_BACAN.

Background: One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates. Also cleaves mouse Nlrp1b allele 1, leading to NLRP1 inflammasome activation, IL1B release and eventually host inflammatory response Miscellaneous LF binds to the heptamer formed by cleaved PA on the host cell membrane. This step is followed by internalization of the heterooligomeric complex by receptor-mediated endocytosis. LeTx requires passage through an acidic vesicle for activity, at acidic pH , as the pore is inserted into the membrane, LF is translocated and reaches its cytosolic targets. LF is probably directly involved in its routing, by interacting with the lipid membrane. This interaction could involve a conformational change of LF and/or an oligomerization of the protein. LF may have the capability of partially unfolding in order to cross the membrane. Catalytic activity Preferred amino acids around the cleavage site can be denoted BBBBxHx-|-H, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases. Cofactor Zn2+ Binds 1 zinc ion per subunit.