1t6b

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(New page: 200px<br /> <applet load="1t6b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t6b, resolution 2.50&Aring;" /> '''Crystal structure o...)
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[[Image:1t6b.gif|left|200px]]<br />
 
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<applet load="1t6b" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1t6b, resolution 2.50&Aring;" />
 
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'''Crystal structure of B. anthracis Protective Antigen complexed with human Anthrax toxin receptor'''<br />
 
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==Overview==
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==Crystal structure of B. anthracis Protective Antigen complexed with human Anthrax toxin receptor==
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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.
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<StructureSection load='1t6b' size='340' side='right'caption='[[1t6b]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1t6b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T6B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T6B FirstGlance]. <br>
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Known diseases associated with this structure: Fibromatosis, juvenile hyaline OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608041 608041]], Hyalinosis, infantile systemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608041 608041]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
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==About this Structure==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t6b OCA], [https://pdbe.org/1t6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t6b RCSB], [https://www.ebi.ac.uk/pdbsum/1t6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t6b ProSAT]</span></td></tr>
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1T6B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA, MN, NA and PG4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1T6B OCA].
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</table>
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== Function ==
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==Reference==
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[https://www.uniprot.org/uniprot/PAG_BACAN 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.
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15243628 15243628]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t6/1t6b_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1t6b ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Bacillus anthracis]]
[[Category: Bacillus anthracis]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Bankston, L.A.]]
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[[Category: Bankston LA]]
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[[Category: Leppla, S.H.]]
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[[Category: Leppla SH]]
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[[Category: Liddington, R.C.]]
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[[Category: Liddington RC]]
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[[Category: Santelli, E.]]
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[[Category: Santelli E]]
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[[Category: CA]]
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[[Category: MN]]
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[[Category: NA]]
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[[Category: PG4]]
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[[Category: bacillus anthracis; anthrax toxin; x-ray crystallography]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:21:23 2007''
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Current revision

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

PDB ID 1t6b

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