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The structure of the GPCR-G-protein complex
Structural highlights
FunctionPE2R3_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][1] [2] [3] [4] [5] Publication Abstract from PubMedProstaglandin receptors have been implicated in a wide range of functions, including inflammation, immune response, reproduction, and cancer. Our group has previously determined the crystal structure of the active-like EP3 bound to its endogenous agonist, prostaglandin E(2). Here, we present the single-particle cryoelectron microscopy (cryo-EM) structure of the human EP3-G(i) signaling complex at a resolution of 3.4 A. The structure reveals the binding mode of G(i) to EP3 and the structural changes induced in EP3 by G(i) binding. In addition, we compare the structure of the EP3-G(i) complex with other subtypes of prostaglandin receptors (EP2 and EP4) bound to G(s) that have been previously reported and examine the differences in amino acid composition at the receptor-G protein interface. Mutational analysis reveals that the selectivity of the G protein depends on specific amino acid residues in the second intracellular loop and TM5. Structural insights into the G protein selectivity revealed by the human EP3-G(i) signaling complex.,Suno R, Sugita Y, Morimoto K, Takazaki H, Tsujimoto H, Hirose M, Suno-Ikeda C, Nomura N, Hino T, Inoue A, Iwasaki K, Kato T, Iwata S, Kobayashi T Cell Rep. 2022 Sep 13;40(11):111323. doi: 10.1016/j.celrep.2022.111323. PMID:36103815[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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