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| | <SX load='6dlw' size='340' side='right' viewer='molstar' caption='[[6dlw]], [[Resolution|resolution]] 3.90Å' scene=''> | | <SX load='6dlw' size='340' side='right' viewer='molstar' caption='[[6dlw]], [[Resolution|resolution]] 3.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dlw]] is a 22 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DLW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DLW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dlw]] is a 22 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=6DLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DLW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6dlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dlw OCA], [http://pdbe.org/6dlw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dlw RCSB], [http://www.ebi.ac.uk/pdbsum/6dlw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dlw 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=6dlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dlw OCA], [https://pdbe.org/6dlw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dlw RCSB], [https://www.ebi.ac.uk/pdbsum/6dlw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dlw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CO9_HUMAN CO9_HUMAN]] Age-related macular degeneration;Immunodeficiency due to a late component of complements deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/CO9_HUMAN CO9_HUMAN] Age-related macular degeneration;Immunodeficiency due to a late component of complements deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CO9_HUMAN CO9_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. C9 is the pore-forming subunit of the MAC. | + | [https://www.uniprot.org/uniprot/CO9_HUMAN CO9_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. C9 is the pore-forming subunit of the MAC. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dunstone, M A]] | + | [[Category: Dunstone MA]] |
| - | [[Category: Law, R H.P]] | + | [[Category: Law RHP]] |
| - | [[Category: Spicer, B A]] | + | [[Category: Spicer BA]] |
| - | [[Category: Complement]]
| + | |
| - | [[Category: Em]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Pore]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Disease
CO9_HUMAN Age-related macular degeneration;Immunodeficiency due to a late component of complements deficiency. Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
CO9_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. C9 is the pore-forming subunit of the MAC.
Publication Abstract from PubMed
Complement component 9 (C9) functions as the pore-forming component of the Membrane Attack Complex (MAC). During MAC assembly, multiple copies of C9 are sequentially recruited to membrane associated C5b8 to form a pore. Here we determined the 2.2 A crystal structure of monomeric murine C9 and the 3.9 A resolution cryo EM structure of C9 in a polymeric assembly. Comparison with other MAC proteins reveals that the first transmembrane region (TMH1) in monomeric C9 is uniquely positioned and functions to inhibit its self-assembly in the absence of C5b8. We further show that following C9 recruitment to C5b8, a conformational change in TMH1 permits unidirectional and sequential binding of additional C9 monomers to the growing MAC. This mechanism of pore formation contrasts with related proteins, such as perforin and the cholesterol dependent cytolysins, where it is believed that pre-pore assembly occurs prior to the simultaneous release of the transmembrane regions.
The first transmembrane region of complement component-9 acts as a brake on its self-assembly.,Spicer BA, Law RHP, Caradoc-Davies TT, Ekkel SM, Bayly-Jones C, Pang SS, Conroy PJ, Ramm G, Radjainia M, Venugopal H, Whisstock JC, Dunstone MA Nat Commun. 2018 Aug 15;9(1):3266. doi: 10.1038/s41467-018-05717-0. PMID:30111885[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Spicer BA, Law RHP, Caradoc-Davies TT, Ekkel SM, Bayly-Jones C, Pang SS, Conroy PJ, Ramm G, Radjainia M, Venugopal H, Whisstock JC, Dunstone MA. The first transmembrane region of complement component-9 acts as a brake on its self-assembly. Nat Commun. 2018 Aug 15;9(1):3266. doi: 10.1038/s41467-018-05717-0. PMID:30111885 doi:http://dx.doi.org/10.1038/s41467-018-05717-0
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