{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Harris JA"],"funding":["Kinship Foundation","Human Frontier Science Program","Department of Education and Training | Australian Research Council","Pew Charitable Trusts","NCRR NIH HHS","Howard Hughes Medical Institute","Department of Health | National Health and Medical Research Council","NIGMS NIH HHS","NIH HHS","U.S. Department of Health &amp; Human Services | National Institutes of Health","National Science Foundation","Esther A. and Joseph Klingenstein Fund"],"pagination":["109-115"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8712391"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(1)"],"pubmed_abstract":["The neuropeptide substance P (SP) is important in pain and inflammation. SP activates the neurokinin-1 receptor (NK1R) to signal via G<sub>q</sub> and G<sub>s</sub> proteins. Neurokinin A also activates NK1R, but leads to selective G<sub>q</sub> signaling. How two stimuli yield distinct G protein signaling at the same G protein-coupled receptor remains unclear. We determined cryogenic-electron microscopy structures of active NK1R bound to SP or the G<sub>q</sub>-biased peptide SP6-11. Peptide interactions deep within NK1R are critical for receptor activation. Conversely, interactions between SP and NK1R extracellular loops are required for potent G<sub>s</sub> signaling but not G<sub>q</sub> signaling. Molecular dynamics simulations showed that these superficial contacts restrict SP flexib"],"journal":["Nature chemical biology"],"pubmed_title":["Selective G protein signaling driven by substance P-neurokinin receptor dynamics."],"pmcid":["PMC8712391"],"funding_grant_id":["DP5 OD023048","S10OD021741","U24 GM129541","DP5OD023048","R01 GM127359","S10OD020054","APP1196951","S10 RR026814","APP1138448","LT000916/2018-L","DE170100152","R01GM127359","S10 OD020054","T32 GM008284","2034836","R35 GM140847","S10 OD021741"],"pubmed_authors":["Thal DM","Gondin AB","Harris JA","Veldhuis NA","Manglik A","Faust B","Suomivuori CM","Dror RO","Cheng Y","Damgen MA"],"additional_accession":[]},"is_claimable":false,"name":"Selective G protein signaling driven by substance P-neurokinin receptor dynamics.","description":"The neuropeptide substance P (SP) is important in pain and inflammation. SP activates the neurokinin-1 receptor (NK1R) to signal via G<sub>q</sub> and G<sub>s</sub> proteins. Neurokinin A also activates NK1R, but leads to selective G<sub>q</sub> signaling. How two stimuli yield distinct G protein signaling at the same G protein-coupled receptor remains unclear. We determined cryogenic-electron microscopy structures of active NK1R bound to SP or the G<sub>q</sub>-biased peptide SP6-11. Peptide interactions deep within NK1R are critical for receptor activation. Conversely, interactions between SP and NK1R extracellular loops are required for potent G<sub>s</sub> signaling but not G<sub>q</sub> signaling. Molecular dynamics simulations showed that these superficial contacts restrict SP flexib","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2026-05-31T05:02:55.533Z","creation":"2025-02-19T01:54:27.39Z"},"accession":"S-EPMC8712391","cross_references":{"pubmed":["34711980"],"doi":["10.1038/s41589-021-00890-8"]}}