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| | ==Crystal structure of the mouse C5a-desArg anaphylatoxin== | | ==Crystal structure of the mouse C5a-desArg anaphylatoxin== |
| - | <StructureSection load='4p3b' size='340' side='right' caption='[[4p3b]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='4p3b' size='340' side='right'caption='[[4p3b]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4p3b]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P3B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P3B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4p3b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P3B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4p3a|4p3a]], [[4p39|4p39]]</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=4p3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p3b OCA], [https://pdbe.org/4p3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p3b RCSB], [https://www.ebi.ac.uk/pdbsum/4p3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p3b ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C5, Hc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4p3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p3b OCA], [http://pdbe.org/4p3b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p3b RCSB], [http://www.ebi.ac.uk/pdbsum/4p3b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p3b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CO5_MOUSE CO5_MOUSE]] 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_MOUSE CO5_MOUSE] 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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4p3b" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4p3b" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Complement C5 3D structures|Complement C5 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Andersen, G R]] | + | [[Category: Mus musculus]] |
| - | [[Category: Schatz-Jakobsen, J A]] | + | [[Category: Andersen GR]] |
| - | [[Category: Yatime, L]] | + | [[Category: Schatz-Jakobsen JA]] |
| - | [[Category: C5a]]
| + | [[Category: Yatime L]] |
| - | [[Category: Complement anaphylatoxin]]
| + | |
| - | [[Category: Four-helix bundle]]
| + | |
| - | [[Category: Gpcr agonist]] | + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
CO5_MOUSE 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.
See Also
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
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