{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:43:55Z","timestamp":1791297835915,"version":"4.1.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,8,28]]},"abstract":"<jats:p>\n                    Incretins, endogenous polypeptide hormones released in response to food intake, potentiate insulin secretion from pancreatic \u03b2 cells after oral glucose ingestion (the incretin effect). This response is signaled by the two peptide hormones glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) and glucagon-like peptide 1 through binding and activation of their cognate class 2 G protein-coupled receptors (GPCRs). Because the incretin effect is lost or significantly reduced in patients with type 2 diabetes mellitus, glucagon-like peptide 1 and GIP have attracted considerable attention for their potential in antidiabetic therapy. A paucity of structural information precludes a detailed understanding of the processes of hormone binding and receptor activation, hampering efforts to develop novel pharmaceuticals. Here we report the crystal structure of the complex of human GIP receptor extracellular domain (ECD) with its agonist, the incretin GIP\n                    <jats:sub>1\u201342<\/jats:sub>\n                    . The hormone binds in an \u03b1-helical conformation in a surface groove of the ECD largely through hydrophobic interactions. The N-terminal ligand residues would remain free to interact with other parts of the receptor. Thermodynamic data suggest that binding is concomitant with structural organization of the hormone, resulting in a complex mode of receptor\u2013ligand recognition. The presentation of a well structured, \u03b1-helical ligand by the ECD is expected to be conserved among other hormone receptors of this class.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0706404104","type":"journal-article","created":{"date-parts":[[2007,8,21]],"date-time":"2007-08-21T20:48:23Z","timestamp":1187729303000},"page":"13942-13947","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":220,"title":["Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor"],"prefix":"10.1073","volume":"104","author":[{"given":"Christoph","family":"Parthier","sequence":"first","affiliation":[{"name":"*Institut f\u00fcr Biochemie und Biotechnologie and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kleinschmidt","sequence":"additional","affiliation":[{"name":"Probiodrug AG, Biocenter Halle, D-06120 Halle (Saale), 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