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2qqh

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(New page: 200px<br /> <applet load="2qqh" size="450" color="white" frame="true" align="right" spinBox="true" caption="2qqh, resolution 2.50&Aring;" /> '''Structure of C8a-MA...)
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[[Image:2qqh.gif|left|200px]]<br />
 
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<applet load="2qqh" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2qqh, resolution 2.50&Aring;" />
 
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'''Structure of C8a-MACPF reveals mechanism of membrane attack in complement immune defense'''<br />
 
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==Overview==
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==Structure of C8a-MACPF reveals mechanism of membrane attack in complement immune defense==
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Membrane attack is important for mammalian immune defense against invading, microorganisms and infected host cells. Proteins of the complement, membrane attack complex (MAC) and the protein perforin share a common, MACPF domain that is responsible for membrane insertion and pore, formation. We determined the crystal structure of the MACPF domain of, complement component C8alpha at 2.5 angstrom resolution and show that it, is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins. The structure displays two regions that, (in the bacterial cytolysins) refold into transmembrane beta hairpins, forming the lining of a barrel pore. Local hydrophobicity explains why, C8alpha is the first complement protein to insert into the membrane. The, size of the MACPF domain is consistent with known C9 pore sizes. These, data imply that these mammalian and bacterial cytolytic proteins share a, common mechanism of membrane insertion.
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<StructureSection load='2qqh' size='340' side='right'caption='[[2qqh]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2qqh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QQH FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C8A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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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=2qqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qqh OCA], [https://pdbe.org/2qqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qqh RCSB], [https://www.ebi.ac.uk/pdbsum/2qqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qqh ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[https://www.uniprot.org/uniprot/CO8A_HUMAN CO8A_HUMAN]] Defects in C8A are a cause of complement component 8 deficiency type 1 (C8D1) [MIM:[https://omim.org/entry/613790 613790]]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.
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== Function ==
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[[https://www.uniprot.org/uniprot/CO8A_HUMAN CO8A_HUMAN]] Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C8A inserts into the target membrane, but does not form pores by itself.<ref>PMID:7440581</ref> <ref>PMID:17872444</ref>
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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/qq/2qqh_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=2qqh ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Membrane attack is important for mammalian immune defense against invading microorganisms and infected host cells. Proteins of the complement membrane attack complex (MAC) and the protein perforin share a common MACPF domain that is responsible for membrane insertion and pore formation. We determined the crystal structure of the MACPF domain of complement component C8alpha at 2.5 angstrom resolution and show that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins. The structure displays two regions that (in the bacterial cytolysins) refold into transmembrane beta hairpins, forming the lining of a barrel pore. Local hydrophobicity explains why C8alpha is the first complement protein to insert into the membrane. The size of the MACPF domain is consistent with known C9 pore sizes. These data imply that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion.
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==Disease==
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Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense.,Hadders MA, Beringer DX, Gros P Science. 2007 Sep 14;317(5844):1552-4. PMID:17872444<ref>PMID:17872444</ref>
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Known disease associated with this structure: C8 deficiency, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120950 120950]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2QQH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and NI as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2QQH OCA].
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</div>
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<div class="pdbe-citations 2qqh" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense., Hadders MA, Beringer DX, Gros P, Science. 2007 Sep 14;317(5844):1552-4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17872444 17872444]
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<references/>
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[[Category: Homo sapiens]]
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__TOC__
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[[Category: Single protein]]
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</StructureSection>
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[[Category: Gros, P.]]
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[[Category: Human]]
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[[Category: Hadders, M.A.]]
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[[Category: Large Structures]]
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[[Category: NI]]
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[[Category: Gros, P]]
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[[Category: SO4]]
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[[Category: Hadders, M A]]
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[[Category: cleavage on pair of basic residues]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: complement alternate pathway]]
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[[Category: Complement alternate pathway]]
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[[Category: complement pathway]]
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[[Category: Complement pathway]]
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[[Category: cytolysis]]
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[[Category: Cytolysis]]
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[[Category: egf-like domain]]
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[[Category: Egf-like domain]]
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[[Category: glycoprotein]]
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[[Category: Glycoprotein]]
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[[Category: immune response]]
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[[Category: Immune response]]
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[[Category: immune system]]
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[[Category: Immune system]]
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[[Category: innate immunity]]
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[[Category: Innate immunity]]
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[[Category: macpf]]
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[[Category: Macpf]]
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[[Category: membrane attack complex]]
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[[Category: Membrane attack complex]]
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[[Category: membrane perforation]]
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[[Category: Membrane perforation]]
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[[Category: membrane protein]]
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[[Category: Membrane protein]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: secreted]]
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[[Category: Secreted]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:34:42 2007''
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Current revision

Structure of C8a-MACPF reveals mechanism of membrane attack in complement immune defense

PDB ID 2qqh

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