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2qos

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Revision as of 07:31, 25 October 2017

Crystal structure of complement protein C8 in complex with a peptide containing the C8 binding site on C8

Structural highlights

2qos is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1lf7, 1iw2, 2ove, 2ova, 2ovd
Gene:	C8G (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

[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. [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]

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

Human C8 is one of five complement components (C5b, C6, C7, C8 and C9) that interact to form the cytolytic membrane attack complex. It contains three genetically distinct subunits; C8alpha and C8gamma form a disulfide-linked C8alpha-gamma heterodimer that is noncovalently associated with C8beta. The C8alpha subunit is homologous to C8beta, C6, C7 and C9 and together they form the MAC family of proteins. By contrast, C8gamma is the only lipocalin in the complement system. Like other lipocalins, it has a core beta-barrel structure forming a calyx with a distinct binding pocket for a small and as yet unidentified ligand. The binding site on C8alpha for C8gamma was previously localized to a 19-residue segment which contains an insertion (indel) that is unique to C8alpha. Included in the indel is C8alpha Cys 164 which links to Cys 40 in C8gamma. In the present study, C8gamma containing a C40A substitution was co-crystallized with a synthetic indel peptide containing the equivalent of a C8alpha C164A substitution. The X-ray crystal structure shows that the indel peptide completely fills the upper portion of the putative C8gamma ligand binding pocket and is in contact with all four loops at the calyx entrance. The lower part of the C8gamma cavity is either unoccupied or contains disordered solvent. The validity of the structure is supported by the spatial arrangement of C8alpha Ala 164 in the peptide and C8gamma Ala 40, which are within disulfide-bonding distance of each other. Corresponding studies in solution indicate the C8gamma ligand binding site is also occupied by the indel segment of C8alpha in whole C8. These results suggest a role for C8alpha in regulating access to the putative C8gamma ligand binding site.

Crystal structure of complement protein C8gamma in complex with a peptide containing the C8gamma binding site on C8alpha: implications for C8gamma ligand binding.,Lovelace LL, Chiswell B, Slade DJ, Sodetz JM, Lebioda L Mol Immunol. 2008 Feb;45(3):750-6. Epub 2007 Aug 9. PMID:17692377^[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, Chiswell B, Slade DJ, Sodetz JM, Lebioda L. Crystal structure of complement protein C8gamma in complex with a peptide containing the C8gamma binding site on C8alpha: implications for C8gamma ligand binding. Mol Immunol. 2008 Feb;45(3):750-6. Epub 2007 Aug 9. PMID:17692377 doi:10.1016/j.molimm.2007.06.359

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qos"

@@ Line 1: / Line 1: @@
 ==Crystal structure of complement protein C8 in complex with a peptide containing the C8 binding site on C8==
 <StructureSection load='2qos' size='340' side='right' caption='[[2qos]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lf7|1lf7]], [[1iw2|1iw2]], [[2ove|2ove]], [[2ova|2ova]], [[2ovd|2ovd]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C8G ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2qos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qos OCA], [http://pdbe.org/2qos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qos RCSB], [http://www.ebi.ac.uk/pdbsum/2qos PDBsum]</span></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=2qos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qos OCA], [http://pdbe.org/2qos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qos RCSB], [http://www.ebi.ac.uk/pdbsum/2qos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qos ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 52: / Line 53: @@
 [[Category: Lipocalin]]
 [[Category: Membrane attack complex]]
+[[Category: Polymorphism]]
 [[Category: Secreted]]

2qos

From Proteopedia

Revision as of 07:31, 25 October 2017

Crystal structure of complement protein C8 in complex with a peptide containing the C8 binding site on C8

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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