6ak3
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PE2R3_HUMAN PE2R3_HUMAN]] Receptor for prostaglandin E2 (PGE2) (PubMed:8307176, PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium (PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity).[UniProtKB:P30557]<ref>PMID:7883006</ref> <ref>PMID:7981210</ref> <ref>PMID:8117308</ref> <ref>PMID:8135729</ref> <ref>PMID:8307176</ref> | [[http://www.uniprot.org/uniprot/PE2R3_HUMAN PE2R3_HUMAN]] Receptor for prostaglandin E2 (PGE2) (PubMed:8307176, PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium (PubMed:7883006, PubMed:8117308, PubMed:8135729, PubMed:7981210). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity).[UniProtKB:P30557]<ref>PMID:7883006</ref> <ref>PMID:7981210</ref> <ref>PMID:8117308</ref> <ref>PMID:8135729</ref> <ref>PMID:8307176</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Prostaglandin E receptor EP4, a G-protein-coupled receptor, is involved in disorders such as cancer and autoimmune disease. Here, we report the crystal structure of human EP4 in complex with its antagonist ONO-AE3-208 and an inhibitory antibody at 3.2 A resolution. The structure reveals that the extracellular surface is occluded by the extracellular loops and that the antagonist lies at the interface with the lipid bilayer, proximal to the highly conserved Arg316 residue in the seventh transmembrane domain. Functional and docking studies demonstrate that the natural agonist PGE2 binds in a similar manner. This structural information also provides insight into the ligand entry pathway from the membrane bilayer to the EP4 binding pocket. Furthermore, the structure reveals that the antibody allosterically affects the ligand binding of EP4. These results should facilitate the design of new therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family. | ||
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| + | Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interface.,Toyoda Y, Morimoto K, Suno R, Horita S, Yamashita K, Hirata K, Sekiguchi Y, Yasuda S, Shiroishi M, Shimizu T, Urushibata Y, Kajiwara Y, Inazumi T, Hotta Y, Asada H, Nakane T, Shiimura Y, Nakagita T, Tsuge K, Yoshida S, Kuribara T, Hosoya T, Sugimoto Y, Nomura N, Sato M, Hirokawa T, Kinoshita M, Murata T, Takayama K, Yamamoto M, Narumiya S, Iwata S, Kobayashi T Nat Chem Biol. 2019 Jan;15(1):18-26. doi: 10.1038/s41589-018-0131-3. Epub 2018, Dec 3. PMID:30510193<ref>PMID:30510193</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ak3" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 08:47, 19 December 2018
Crystal structure of the human prostaglandin E receptor EP3 bound to prostaglandin E2
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