8hk5: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8hk5]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HK5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[8hk5]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HK5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></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=8hk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hk5 OCA], [https://pdbe.org/8hk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hk5 RCSB], [https://www.ebi.ac.uk/pdbsum/8hk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hk5 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=8hk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hk5 OCA], [https://pdbe.org/8hk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hk5 RCSB], [https://www.ebi.ac.uk/pdbsum/8hk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hk5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref>  
[https://www.uniprot.org/uniprot/C5AR1_HUMAN C5AR1_HUMAN] Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a (PubMed:1847994, PubMed:8182049, PubMed:7622471, PubMed:9553099, PubMed:10636859, PubMed:15153520). The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events (PubMed:8182049, PubMed:7622471, PubMed:9553099). Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production (PubMed:10636859, PubMed:15153520).<ref>PMID:10636859</ref> <ref>PMID:15153520</ref> <ref>PMID:1847994</ref> <ref>PMID:7622471</ref> <ref>PMID:8182049</ref> <ref>PMID:9553099</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR1 signaling lead to multiple inflammatory disorders, including sepsis, asthma and acute respiratory distress syndrome. The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR1 remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo-C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understanding of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders.
 
Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins.,Wang Y, Liu W, Xu Y, He X, Yuan Q, Luo P, Fan W, Zhu J, Zhang X, Cheng X, Jiang Y, Xu HE, Zhuang Y Nat Chem Biol. 2023 Nov;19(11):1351-1360. doi: 10.1038/s41589-023-01339-w. Epub , 2023 May 11. PMID:37169960<ref>PMID:37169960</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hk5" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 10:21, 21 November 2024

C5aR1-Gi-C5a protein complexC5aR1-Gi-C5a protein complex

Structural highlights

8hk5 is a 5 chain structure with sequence from Bos taurus, Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

C5AR1_HUMAN Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a (PubMed:1847994, PubMed:8182049, PubMed:7622471, PubMed:9553099, PubMed:10636859, PubMed:15153520). The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events (PubMed:8182049, PubMed:7622471, PubMed:9553099). Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production (PubMed:10636859, PubMed:15153520).[1] [2] [3] [4] [5] [6]

Publication Abstract from PubMed

The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR1 signaling lead to multiple inflammatory disorders, including sepsis, asthma and acute respiratory distress syndrome. The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR1 remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo-C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understanding of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders.

Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins.,Wang Y, Liu W, Xu Y, He X, Yuan Q, Luo P, Fan W, Zhu J, Zhang X, Cheng X, Jiang Y, Xu HE, Zhuang Y Nat Chem Biol. 2023 Nov;19(11):1351-1360. doi: 10.1038/s41589-023-01339-w. Epub , 2023 May 11. PMID:37169960[7]

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

References

  1. ↑ Christophe T, Rabiet MJ, Tardif M, Milcent MD, Boulay F. Human complement 5a (C5a) anaphylatoxin receptor (CD88) phosphorylation sites and their specific role in receptor phosphorylation and attenuation of G protein-mediated responses. Desensitization of C5a receptor controls superoxide production but not receptor sequestration in HL-60 cells. J Biol Chem. 2000 Jan 21;275(3):1656-64. PMID:10636859
  2. ↑ Postma B, Poppelier MJ, van Galen JC, Prossnitz ER, van Strijp JA, de Haas CJ, van Kessel KP. Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol. 2004 Jun 1;172(11):6994-7001. PMID:15153520
  3. ↑ Gerard NP, Gerard C. The chemotactic receptor for human C5a anaphylatoxin. Nature. 1991 Feb 14;349(6310):614-7. PMID:1847994 doi:http://dx.doi.org/10.1038/349614a0
  4. ↑ Monk PN, Barker MD, Partridge LJ, Pease JE. Mutation of glutamate 199 of the human C5a receptor defines a binding site for ligand distinct from the receptor N terminus. J Biol Chem. 1995 Jul 14;270(28):16625-9. PMID:7622471
  5. ↑ DeMartino JA, Van Riper G, Siciliano SJ, Molineaux CJ, Konteatis ZD, Rosen H, Springer MS. The amino terminus of the human C5a receptor is required for high affinity C5a binding and for receptor activation by C5a but not C5a analogs. J Biol Chem. 1994 May 20;269(20):14446-50. PMID:8182049
  6. ↑ Chen Z, Zhang X, Gonnella NC, Pellas TC, Boyar WC, Ni F. Residues 21-30 within the extracellular N-terminal region of the C5a receptor represent a binding domain for the C5a anaphylatoxin. J Biol Chem. 1998 Apr 24;273(17):10411-9. PMID:9553099
  7. ↑ Wang Y, Liu W, Xu Y, He X, Yuan Q, Luo P, Fan W, Zhu J, Zhang X, Cheng X, Jiang Y, Xu HE, Zhuang Y. Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. Nat Chem Biol. 2023 Nov;19(11):1351-1360. PMID:37169960 doi:10.1038/s41589-023-01339-w

8hk5, resolution 3.00Å

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