Human Substance P Interactions with G Protein-Coupled Receptor NK1R Observed by NMR in Solution.

ABSTRACT: Neurokinin 1 receptor (NK1R) is a class A G protein-coupled receptor (GPCR) that interacts with the endogenous undecapeptide agonist Substance P (SP) to activate its role in key physiological processes such as nausea, inflammation, and neurological disorders. Structure determinations by cryogenic electron microscopy (cryo-EM) for NK1R with SP bound provided high-quality views of the bulk of these complexes but failed to observe the N-terminal peptide segments of both components. Here, ¹⁹F-NMR spectroscopy was combined with function assays to explore the impact of these chain ends on structure and function. The ¹⁹F-NMR probe 3-trifluoromethyl-l-phenylalanine (mtfF) was introduced into the SP sequence positions 0, 3, 5, 7, and 8 and observed in aqueous solution,

SUBMITTER: Ge H 

PROVIDER: S-EPMC12679638 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature