Sandbox Reserved 1646: Difference between revisions
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=== General structure === | === General structure === | ||
GnRH1R has the overall architecture of seven canonical transmembrane (TM) helices with connecting extra- and intracellular loop domains (ECL/ICL) similar to [https://en.wikipedia.org/wiki/Rhodopsin-like_receptors rhodopsin like receptors]. However, it lacks the typically occurring cytoplasmic C-terminal helix and has an unusual ligand binding mode. The structural variation between existing GnRHR Typ I, II and III in different species has been analyzed <ref>DOI: 10.1210/er.2003-0002</ref>. First crystallographic structure analysis of human GnGH1R serve the investigation of the molecular mechanism of the receptor<ref>DOI: 10.1038/s41467-020-19109-w</ref>. In this analysis the GnRH1R contains certain modifications: ICL3 (aa 243-256) is replaced by the <scene name='86/868179/ | GnRH1R has the overall architecture of seven canonical transmembrane (TM) helices with connecting extra- and intracellular loop domains (ECL/ICL) similar to [https://en.wikipedia.org/wiki/Rhodopsin-like_receptors rhodopsin like receptors]. However, it lacks the typically occurring cytoplasmic C-terminal helix and has an unusual ligand binding mode. The structural variation between existing GnRHR Typ I, II and III in different species has been analyzed <ref>DOI: 10.1210/er.2003-0002</ref>. First crystallographic structure analysis of human GnGH1R serve the investigation of the molecular mechanism of the receptor<ref>DOI: 10.1038/s41467-020-19109-w</ref>. In this analysis the GnRH1R contains certain modifications: ICL3 (aa 243-256) is replaced by the <scene name='86/868179/Abysi_glycogen_synthase/1'>''Pyrococcus abysi'' glycogen synthase</scene>, it is in a complex with the antagonistic drug <scene name='86/868179/Elagolix/4'>elagolix</scene>, and remains in inactive conformation in respect to [https://en.wikipedia.org/wiki/G_protein G protein] coupling. | ||
In this conformation, the ECL2 of GnRH1R forms an <scene name='86/868179/S-interactions/7'>extended β-hairpin</scene> and is anchored to the extracellular tip of TM3 through a conserved disulfide bond between residues C114 and C196 in ECL2. | In this conformation, the ECL2 of GnRH1R forms an <scene name='86/868179/S-interactions/7'>extended β-hairpin</scene> and is anchored to the extracellular tip of TM3 through a conserved disulfide bond between residues C114 and C196 in ECL2. | ||
Following structural highlights are different to receptors of this family: The conserved D138-R183-Y3.51 motif is in fact the <scene name='86/868179/Motiv138-140/1'>D3.49-R3.50-S3.51 motif</scene> in GnRH1R. An intrahelical salt bridge is observed between D138 and R139, as well as a polar interaction between R139 and T265 6.33 (This restricts the outward movement of those TMs associated with GPCR activation). The <scene name='86/868179/N-terminus/1'>N-terminal region</scene> (aa 18–33) before TM1 is well folded and appears inserted into the orthostatic binding cavity. | Following structural highlights are different to receptors of this family: The conserved D138-R183-Y3.51 motif is in fact the <scene name='86/868179/Motiv138-140/1'>D3.49-R3.50-S3.51 motif</scene> in GnRH1R. An intrahelical salt bridge is observed between D138 and R139, as well as a polar interaction between R139 and T265 6.33 (This restricts the outward movement of those TMs associated with GPCR activation). The <scene name='86/868179/N-terminus/1'>N-terminal region</scene> (aa 18–33) before TM1 is well folded and appears inserted into the orthostatic binding cavity. | ||
