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| | ==Structure of complement C5 in complex with SSL7== | | ==Structure of complement C5 in complex with SSL7== |
| - | <StructureSection load='3kls' size='340' side='right' caption='[[3kls]], [[Resolution|resolution]] 3.60Å' scene=''> | + | <StructureSection load='3kls' size='340' side='right'caption='[[3kls]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kls]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staar Staar]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KLS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kls]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_MRSA252 Staphylococcus aureus subsp. aureus MRSA252]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KLS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</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">X-ray diffraction, [[Resolution|Resolution]] 3.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cu7|3cu7]], [[2qej|2qej]], [[3km9|3km9]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kls OCA], [http://pdbe.org/3kls PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kls RCSB], [http://www.ebi.ac.uk/pdbsum/3kls PDBsum]</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=3kls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kls OCA], [https://pdbe.org/3kls PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kls RCSB], [https://www.ebi.ac.uk/pdbsum/3kls PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kls ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN]] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:[http://omim.org/entry/609536 609536]]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele (PubMed:15995705). | + | [https://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:[https://omim.org/entry/609536 609536]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele (PubMed:15995705). |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN]] Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled. Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis). | + | [https://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN] Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled. Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/3kls_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/3kls_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Complement C5|Complement C5]] | + | *[[Complement C5 3D structures|Complement C5 3D structures]] |
| - | *[[Exotoxin|Exotoxin]] | + | *[[Exotoxin 3D structures|Exotoxin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Staar]] | + | [[Category: Large Structures]] |
| - | [[Category: Andersen, G R]] | + | [[Category: Staphylococcus aureus subsp. aureus MRSA252]] |
| - | [[Category: Bjerre, M]] | + | [[Category: Andersen GR]] |
| - | [[Category: Christensen, J B]] | + | [[Category: Bjerre M]] |
| - | [[Category: Fraser, J D]] | + | [[Category: Christensen JB]] |
| - | [[Category: Fredslund, F]] | + | [[Category: Fraser JD]] |
| - | [[Category: Gordon, N]] | + | [[Category: Fredslund F]] |
| - | [[Category: Hermans, S]] | + | [[Category: Gordon N]] |
| - | [[Category: Jackson, N]] | + | [[Category: Hermans S]] |
| - | [[Category: Jensen, M]] | + | [[Category: Jackson N]] |
| - | [[Category: Laursen, N S]] | + | [[Category: Jensen M]] |
| - | [[Category: Lorenz, N]] | + | [[Category: Laursen NS]] |
| - | [[Category: Sottrup-Jensen, L]] | + | [[Category: Lorenz N]] |
| - | [[Category: Spillner, E]] | + | [[Category: Sottrup-Jensen L]] |
| - | [[Category: Wines, B]] | + | [[Category: Spillner E]] |
| - | [[Category: B-grasp domain]]
| + | [[Category: Wines B]] |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Complement alternate pathway]]
| + | |
| - | [[Category: Complement pathway]]
| + | |
| - | [[Category: Cytolysis]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Fn3 domain]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Immune response]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Inflammatory response]]
| + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Membrane attack complex]]
| + | |
| - | [[Category: Ob-fold]]
| + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
Disease
CO5_HUMAN Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:609536. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele (PubMed:15995705).
Function
CO5_HUMAN Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled. Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis).
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
Staphylococcus aureus secretes the SSL7 protein as part of its immune evasion strategy. The protein binds both complement C5 and IgA, yet it is unclear whether SSL7 cross-links these two proteins and, if so, what purpose this serves the pathogen. We have isolated a stable IgA-SSL7-C5 complex, and our crystal structure of the C5-SSL7 complex confirms that binding to C5 occurs exclusively through the C-terminal beta-grasp domain of SSL7 leaving the OB domain free to interact with IgA. SSL7 interacts with C5 >70 A from the C5a cleavage site without inducing significant conformational changes in C5, and efficient inhibition of convertase cleavage of C5 is shown to be IgA dependent. Inhibition of C5a production and bacteriolysis are all shown to require C5 and IgA binding while inhibition of hemolysis is achieved by the C5 binding SSL7 beta-grasp domain alone. These results provide a conceptual and structural basis for the development of a highly specific complement inhibitor preventing only the formation of the lytic membrane attack complex without affecting the important signaling functions of C5a.
Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus.,Laursen NS, Gordon N, Hermans S, Lorenz N, Jackson N, Wines B, Spillner E, Christensen JB, Jensen M, Fredslund F, Bjerre M, Sottrup-Jensen L, Fraser JD, Andersen GR Proc Natl Acad Sci U S A. 2010 Feb 4. PMID:20133685[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Laursen NS, Gordon N, Hermans S, Lorenz N, Jackson N, Wines B, Spillner E, Christensen JB, Jensen M, Fredslund F, Bjerre M, Sottrup-Jensen L, Fraser JD, Andersen GR. Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus. Proc Natl Acad Sci U S A. 2010 Feb 4. PMID:20133685
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