1t6b

Crystal structure of B. anthracis Protective Antigen complexed with human Anthrax toxin receptor

spinqualitylabelsall models 1t6b, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1t6b is a 2 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 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, MN, NA, PG4 Gene: ANTXR2,CMG2 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [ANTR2_HUMAN] Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM:236490]. This autosomal recessive syndrome is similar to JHF, but has an earlier onset and a more severe course. Symptoms appear at birth or within the first months of life, with painful, swollen joint contractures, osteopenia, osteoporosis and livid red hyperpigmentation over bony prominences. Patients develop multiple subcutaneous skin tumors and gingival hypertrophy. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to death within the first 2 years of life. Surviving children may suffer from severely reduced mobility due to joint contractures. Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM:228600]. JHF is an autosomal recessive syndrome that is similar to ISH but takes a milder course. It is characterized by hyaline deposition in the dermis, multiple subcutaneous skin tumors and gingival hypertrophy, followed by progressive joint contractions, osteopenia and osteoporosis that may lead to a severe limitation of mobility. 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. [ANTR2_HUMAN] Necessary for cellular interactions with laminin and the extracellular matrix. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Anthrax toxin consists of the proteins protective antigen (PA), lethal factor (LF) and oedema factor (EF). The first step of toxin entry into host cells is the recognition by PA of a receptor on the surface of the target cell. Subsequent cleavage of receptor-bound PA enables EF and LF to bind and form a heptameric PA63 pre-pore, which triggers endocytosis. Upon acidification of the endosome, PA63 forms a pore that inserts into the membrane and translocates EF and LF into the cytosol. Two closely related host cell receptors, TEM8 and CMG2, have been identified. Both bind to PA with high affinity and are capable of mediating toxicity. Here, we report the crystal structure of the PA-CMG2 complex at 2.5 A resolution. The structure reveals an extensive receptor-pathogen interaction surface mimicking the non-pathogenic recognition of the extracellular matrix by integrins. The binding surface is closely conserved in the two receptors and across species, but is quite different in the integrin domains, explaining the specificity of the interaction. CMG2 engages two domains of PA, and modelling of the receptor-bound PA63 heptamer suggests that the receptor acts as a pH-sensitive brace to ensure accurate and timely membrane insertion. The structure provides new leads for the discovery of anthrax anti-toxins, and should aid the design of cancer therapeutics. Crystal structure of a complex between anthrax toxin and its host cell receptor.,Santelli E, Bankston LA, Leppla SH, Liddington RC Nature. 2004 Aug 19;430(7002):905-8. Epub 2004 Jul 4. PMID:15243628 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Anthrax protective antigen 3D structures

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