4p39

From Proteopedia

(Difference between revisions)

Revision as of 11:08, 11 August 2016

Crystal structure of the human C5aR antagonist C5a-A8

Structural highlights

4p39 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3hqa, 3hqb, 4p3b, 4p3a
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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).

Publication Abstract from PubMed

Complement is an ancient part of the innate immune system that plays a pivotal role in protection against invading pathogens and helps to clear apoptotic and necrotic cells. Upon complement activation, a cascade of proteolytic events generates the complement effectors, including the anaphylatoxins C3a and C5a. Signalling through their cognate G-protein coupled receptors, C3aR and C5aR, leads to a wide range of biological events promoting inflammation at the site of complement activation. The function of anaphylatoxins is regulated by circulating carboxypeptidases that remove their C-terminal arginine residue, yielding C3a-desArg and C5a-desArg. Whereas human C3a and C3a-desArg adopt a canonical four-helix bundle fold, the conformation of human C5a-desArg has recently been described as a three-helix bundle. Here, the crystal structures of an antagonist version of human C5a, A8(Delta71-73), and of murine C5a and C5a-desArg are reported. Whereas A8(Delta71-73) adopts a three-helix bundle conformation similar to human C5a-desArg, the two murine proteins form a four-helix bundle. A cell-based functional assay reveals that murine C5a-desArg, in contrast to its human counterpart, exerts the same level of activition as murine C5a on its cognate receptor. The role of the different C5a conformations is discussed in relation to the differential activation of C5a receptors across species.

Structural and functional characterization of human and murine C5a anaphylatoxins.,Schatz-Jakobsen JA, Yatime L, Larsen C, Petersen SV, Klos A, Andersen GR Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1704-17. doi:, 10.1107/S139900471400844X. Epub 2014 May 30. PMID:24914981^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schatz-Jakobsen JA, Yatime L, Larsen C, Petersen SV, Klos A, Andersen GR. Structural and functional characterization of human and murine C5a anaphylatoxins. Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1704-17. doi:, 10.1107/S139900471400844X. Epub 2014 May 30. PMID:24914981 doi:http://dx.doi.org/10.1107/S139900471400844X

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4p39"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human C5aR antagonist C5a-A8==
 <StructureSection load='4p39' size='340' side='right' caption='[[4p39]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4p39]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P39 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P39 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hqa|3hqa]], [[3hqb|3hqb]], [[4p3b|4p3b]], [[4p3a|4p3a]]</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=4p39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p39 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p39 RCSB], [http://www.ebi.ac.uk/pdbsum/4p39 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=4p39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p39 OCA], [http://pdbe.org/4p39 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p39 RCSB], [http://www.ebi.ac.uk/pdbsum/4p39 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p39 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4p39" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4p39

From Proteopedia

Revision as of 11:08, 11 August 2016

Crystal structure of the human C5aR antagonist C5a-A8

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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