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| | ==Human Complement Membrane Attack Proteins Share a Common Fold with Bacterial Cytolysins== | | ==Human Complement Membrane Attack Proteins Share a Common Fold with Bacterial Cytolysins== |
| - | <StructureSection load='2rd7' size='340' side='right' caption='[[2rd7]], [[Resolution|resolution]] 2.15Å' scene=''> | + | <StructureSection load='2rd7' size='340' side='right'caption='[[2rd7]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2rd7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RD7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RD7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2rd7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RD7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C8A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), C8G ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | <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 Homo sapiens]), C8G ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rd7 OCA], [http://pdbe.org/2rd7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rd7 RCSB], [http://www.ebi.ac.uk/pdbsum/2rd7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rd7 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rd7 OCA], [https://pdbe.org/2rd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rd7 RCSB], [https://www.ebi.ac.uk/pdbsum/2rd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rd7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CO8A_HUMAN CO8A_HUMAN]] Defects in C8A are a cause of complement component 8 deficiency type 1 (C8D1) [MIM:[http://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. | + | [[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. |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/CO8G_HUMAN CO8G_HUMAN]] C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol. | + | [[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> [[https://www.uniprot.org/uniprot/CO8G_HUMAN CO8G_HUMAN]] C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Chruszcz, M]] | | [[Category: Chruszcz, M]] |
| | [[Category: Lebioda, L]] | | [[Category: Lebioda, L]] |
| Structural highlights
Disease
[CO8A_HUMAN] Defects in C8A are a cause of complement component 8 deficiency type 1 (C8D1) [MIM:613790]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.
Function
[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.[1] [2] [CO8G_HUMAN] C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol.
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
C8 is one of five complement proteins that assemble on bacterial membranes to form the lethal pore-like "membrane attack complex" (MAC) of complement. The MAC consists of one C5b, C6, C7, and C8 and 12-18 molecules of C9. C8 is composed of three genetically distinct subunits, C8alpha, C8beta, and C8gamma. The C6, C7, C8alpha, C8beta, and C9 proteins are homologous and together comprise the MAC family of proteins. All contain N- and C-terminal modules and a central 40-kDa membrane attack complex perforin (MACPF) domain that has a key role in forming the MAC pore. Here, we report the 2.5 A resolution crystal structure of human C8 purified from blood. This is the first structure of a MAC family member and of a human MACPF-containing protein. The structure shows the modules in C8alpha and C8beta are located on the periphery of C8 and not likely to interact with the target membrane. The C8gamma subunit, a member of the lipocalin family of proteins that bind and transport small lipophilic molecules, shows no occupancy of its putative ligand-binding site. C8alpha and C8beta are related by a rotation of approximately 22 degrees with only a small translational component along the rotation axis. Evolutionary arguments suggest the geometry of binding between these two subunits is similar to the arrangement of C9 molecules within the MAC pore. This leads to a model of the MAC that explains how C8-C9 and C9-C9 interactions could facilitate refolding and insertion of putative MACPF transmembrane beta-hairpins to form a circular pore.
Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement.,Lovelace LL, Cooper CL, Sodetz JM, Lebioda L J Biol Chem. 2011 May 20;286(20):17585-92. Epub 2011 Mar 25. PMID:21454577[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Steckel EW, York RG, Monahan JB, Sodetz JM. The eighth component of human complement. Purification and physicochemical characterization of its unusual subunit structure. J Biol Chem. 1980 Dec 25;255(24):11997-2005. PMID:7440581
- ↑ Hadders MA, Beringer DX, Gros P. Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. Science. 2007 Sep 14;317(5844):1552-4. PMID:17872444 doi:317/5844/1552
- ↑ Lovelace LL, Cooper CL, Sodetz JM, Lebioda L. Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement. J Biol Chem. 2011 May 20;286(20):17585-92. Epub 2011 Mar 25. PMID:21454577 doi:10.1074/jbc.M111.219766
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