7m8w
From Proteopedia
(Difference between revisions)
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==XFEL crystal structure of the prostaglandin D2 receptor CRTH2 in complex with 15R-methyl-PGD2== | ==XFEL crystal structure of the prostaglandin D2 receptor CRTH2 in complex with 15R-methyl-PGD2== | ||
| - | <StructureSection load='7m8w' size='340' side='right'caption='[[7m8w]]' scene=''> | + | <StructureSection load='7m8w' size='340' side='right'caption='[[7m8w]], [[Resolution|resolution]] 2.61Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M8W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7m8w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M8W FirstGlance]. <br> |
| - | </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=7m8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m8w OCA], [https://pdbe.org/7m8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m8w RCSB], [https://www.ebi.ac.uk/pdbsum/7m8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m8w ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.61Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene>, <scene name='pdbligand=YSS:15R-methyl-prostaglandin+D2'>YSS</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=7m8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m8w OCA], [https://pdbe.org/7m8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m8w RCSB], [https://www.ebi.ac.uk/pdbsum/7m8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m8w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/PD2R2_HUMAN PD2R2_HUMAN] Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses.<ref>PMID:11208866</ref> <ref>PMID:11535533</ref> <ref>PMID:17196174</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Prostaglandin D2 (PGD2) signals through the G protein-coupled receptor (GPCR) CRTH2 to mediate various inflammatory responses. CRTH2 is the only member of the prostanoid receptor family that is phylogenetically distant from others, implying a nonconserved mechanism of lipid action on CRTH2. Here, we report a crystal structure of human CRTH2 bound to a PGD2 derivative, 15R-methyl-PGD2 (15mPGD2), by serial femtosecond crystallography. The structure revealed a "polar group in"-binding mode of 15mPGD2 contrasting the "polar group out"-binding mode of PGE2 in its receptor EP3. Structural comparison analysis suggested that these two lipid-binding modes, associated with distinct charge distributions of ligand-binding pockets, may apply to other lipid GPCRs. Molecular dynamics simulations together with mutagenesis studies also identified charged residues at the ligand entry port that function to capture lipid ligands of CRTH2 from the lipid bilayer. Together, our studies suggest critical roles of charge environment in lipid recognition by GPCRs. | ||
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| + | Molecular basis for lipid recognition by the prostaglandin D2 receptor CRTH2.,Liu H, Deepak RNVK, Shiriaeva A, Gati C, Batyuk A, Hu H, Weierstall U, Liu W, Wang L, Cherezov V, Fan H, Zhang C Proc Natl Acad Sci U S A. 2021 Aug 10;118(32). pii: 2102813118. doi:, 10.1073/pnas.2102813118. PMID:34341104<ref>PMID:34341104</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7m8w" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Escherichia virus T4]] | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cherezov V]] | [[Category: Cherezov V]] | ||
[[Category: Han GW]] | [[Category: Han GW]] | ||
[[Category: Shiriaeva A]] | [[Category: Shiriaeva A]] | ||
Current revision
XFEL crystal structure of the prostaglandin D2 receptor CRTH2 in complex with 15R-methyl-PGD2
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