1V36 Toxin date Oct 29, 2003
title Molecular Model Of The Pore Form Of Anthrax Protective Antigen. Extending Available Biochemical And Crystallographic Data
authors T.L.Nguyen
compound source
Molecule: Protective Antigen, Pa-63
Chain: A, B, C, D, E, F, G
 Organism_scientific: Bacillus Anthracis
Organism_common: Bacteria
methodTheoretical Model
ligand CA enzyme
domain Domain 4 appears to be a separate domain and shows limited contact with the other three domains: it would swing out of the way during membrane insertion. The subdomain 1b is part of the remaining 63-kda fragment (pa63) and contains the binding sites for lp and ef. Domain 2 is a beta-barrel core containing a large flexible loop that has been implicated in membrane insertion and pore formation. There is a chymotrypsin cleavage site in this loop that is required for toxicity. The molecule is folded into four functional domains. It is required for binding to the receptor; the small loop is involved in receptor recognition. Cleavage of the pa monomer releases the subdomain 1a, which is the n-terminal fragment of 20-kda (pa20). Domain 1 contains two calcium ions and the proteolytic activation site. Each domain is required for a particular step in the toxicity process. Domain 3 has a hydrophobic patch thought to be involved in protein-protein interactions.
similarity Belongs to the bacterial binary toxin family.[PA14]
subunit Pa-63 forms heptamers and this oligomerization is required for lf or ef binding. Anthrax toxins are composed of three distinct proteins, a protective antigen (pa), a lethal factor (lf) and an edema factor (ef). This complex is endocytosed by the host. Once activated, at low ph, the heptamer undergoes conformational changes and converts from prepore to pore inserted in the membrane, forming cation-selective channels and triggering the release of lf and ef in the host cytoplasm. None of these is toxic by itself. Pa+lf forms the lethal toxin (letx); pa+ef forms the edema toxin (edtx).
post-translat. modifications The release of pa20 from the remaining receptor-bound pa63 exposes the binding site for ef and lf, and promotes oligomerization and internalization of the protein. Proteolytic activation by furin or a furin-like protease cleaves the protein in two parts, pa-20 and pa-63; the latter is the mature protein. The cleavage occurs at the cell surface and probably in the serum of infected animals as well; both native and cleaved pa are able to bind to the cell receptor.
subcellular loc. Therefore, pa is translocated across the membrane in an unfolded state and then it is folded into its native configuration on the trans side of the membrane, prior to its release to the environment. Secreted through the sec-dependent secretion pathway. Pa requires the extracellular chaperone prsa for efficient folding.
genes BXA0164, GBAA (B. anthracis)
function Pa associated with lf causes death when injected, pa associated with ef produces edema. One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. Pa induces immunity to infection with anthrax. Pa binds to a receptor (atr) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane.
Gene
Ontology
ChainFunctionProcessComponent
F, A, D, C, G, E, B
  • calcium ion binding
  • protein binding
  • metal ion binding
  • pathogenesis
  • extracellular region
    • Primary referenceThree-dimensional model of the pore form of anthrax protective antigen. Structure and biological implications., Nguyen TL, J Biomol Struct Dyn. 2004 Dec;22(3):253-65. PMID:15473701
    Data retrieval
  • Asymmetric unit, PDB entry: [header only] [complete with coordinates] (587 Kb) [Save to disk]
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  • View one-letter amino acid or nucleotide sequence for each chain: [1v36_A] [1v36_C] [1v36_G] [1v36_F] [1v36_E] [1v36_D] [1v36_B]
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