3kwv | pdb_00003kwv

Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers

spinqualitylabelsall models 3kwv, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3kwv is a 6 chain structure with sequence from "bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Gene: pagA ("Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946), lef ("Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946) Activity: Hydrolase, with EC number 3.4.24.83 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PAG_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. 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. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. [LEF_BACAN] 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. Publication Abstract from PubMed The protein transporter anthrax lethal toxin is composed of protective antigen (PA), a transmembrane translocase, and lethal factor (LF), a cytotoxic enzyme. After its assembly into holotoxin complexes, PA forms an oligomeric channel that unfolds LF and translocates it into the host cell. We report the crystal structure of the core of a lethal toxin complex to 3.1-A resolution; the structure contains a PA octamer bound to four LF PA-binding domains (LF(N)). The first alpha-helix and beta-strand of each LF(N) unfold and dock into a deep amphipathic cleft on the surface of the PA octamer, which we call the alpha clamp. The alpha clamp possesses nonspecific polypeptide binding activity and is functionally relevant to efficient holotoxin assembly, PA octamer formation, and LF unfolding and translocation. This structure provides insight into the mechanism of translocation-coupled protein unfolding. Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers.,Feld GK, Thoren KL, Kintzer AF, Sterling HJ, Tang II, Greenberg SG, Williams ER, Krantz BA Nat Struct Mol Biol. 2010 Oct 31. PMID:21037566 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Anthrax lethal factor 3D structures

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