Anthrax toxin: receptor binding, internalization, pore formation, and translocation.
Anthrax toxin consists of three nontoxic proteins that self-assemble at the surface of receptor-bearing mammalian cells or in solution, yielding a series of toxic complexes. Two of the proteins, called Lethal Factor (LF) and Edema Factor (EF), are enzymes that act on cytosolic substrates. The third, termed Protective Antigen (PA), is a multifunctional protein that binds to receptors, orchestrates the assembly and internalization of the complexes, and delivers them to the endosome. There, the PA moiety forms a pore in the endosomal membrane and promotes translocation of LF and EF to the cytosol. Recent advances in understanding the entry process include insights into how PA recognizes its two known receptors and its ligands, LF and EF; how the PA:receptor interaction influences the pH-dependence of pore formation; and how the pore functions in promoting translocation of LF and EF across the endosomal membrane.
Young
John A T
JA
Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. jyoung@salk.edu
Collier
R John
RJ
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D004705:Endocytosis / Q000502:physiology*; D045683:Furin / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D008958:Models, Molecular; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide
C473287:ANTXR1 protein, human; C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D052899:Pore Forming Cytotoxic Proteins; D021122:Protein Subunits; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C030325:anthrax toxin; D010649:Phenylalanine; D045683:Furin