7t6s
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7t6s]] 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 Rattus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T6S FirstGlance]. <br> | <table><tr><td colspan='2'>[[7t6s]] 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 Rattus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T6S FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUI:N-(4-chlorophenyl)-N-[1-methyl-3-oxo-2-phenyl-5-(propan-2-yl)-2,3-dihydro-1H-pyrazol-4-yl]urea'>FUI</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]] 3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUI:N-(4-chlorophenyl)-N-[1-methyl-3-oxo-2-phenyl-5-(propan-2-yl)-2,3-dihydro-1H-pyrazol-4-yl]urea'>FUI</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=7t6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t6s OCA], [https://pdbe.org/7t6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t6s RCSB], [https://www.ebi.ac.uk/pdbsum/7t6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t6s 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=7t6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t6s OCA], [https://pdbe.org/7t6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t6s RCSB], [https://www.ebi.ac.uk/pdbsum/7t6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t6s ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally distinct native peptides and even lipid mediators to either promote or resolve inflammation. Pharmacological targeting of FPRs represents a novel therapeutic approach in treating inflammatory diseases. However, the molecular mechanisms underlying FPR ligand recognition are elusive. We report cryo-EM structures of | + | The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally distinct native peptides and even lipid mediators to either promote or resolve inflammation. Pharmacological targeting of FPRs represents a novel therapeutic approach in treating inflammatory diseases. However, the molecular mechanisms underlying FPR ligand recognition are elusive. We report cryo-EM structures of G(i)-coupled FPR1 and FPR2 bound to a formylpeptide and G(i)-coupled FPR2 bound to two synthetic peptide and small-molecule agonists. Together with mutagenesis data, our structures reveal the molecular mechanism of formylpeptide recognition by FPRs and structural variations of FPR1 and FPR2 leading to their different ligand preferences. Structural analysis also suggests that diverse FPR agonists sample a conserved activation chamber at the bottom of ligand-binding pockets to activate FPRs. Our results provide a basis for rational drug design on FPRs. |
Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2.,Zhuang Y, Wang L, Guo J, Sun D, Wang Y, Liu W, Xu HE, Zhang C Nat Commun. 2022 Feb 25;13(1):1054. doi: 10.1038/s41467-022-28586-0. PMID:35217703<ref>PMID:35217703</ref> | Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2.,Zhuang Y, Wang L, Guo J, Sun D, Wang Y, Liu W, Xu HE, Zhang C Nat Commun. 2022 Feb 25;13(1):1054. doi: 10.1038/s41467-022-28586-0. PMID:35217703<ref>PMID:35217703</ref> | ||
Revision as of 11:32, 23 October 2024
Structure of the human FPR2-Gi complex with compound C43
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