Molecular determinants of neuropeptide-mediated activation mechanisms in tachykinin NK1 and NK2 receptors.

ABSTRACT: Substance P and neurokinin A are closely related neuropeptides belonging to the tachykinin family. Their receptors are neurokinin one receptor (NK1R) and neurokinin two receptor (NK2R), G protein-coupled receptors that transmit G_s and G_q-mediated downstream signaling. We investigate the importance of sequence differences at the bottom of the receptor orthosteric site for activity and selectivity, focusing on residues that closely interact with the C-terminal methionine of the peptide ligands. We identify a conserved serine (NK1R-S297^7.45) and the position of the tryptophan residue within the canonical "toggle switch" motif, CWxP of TM6, neighboring a phenylalanine in NK1R (NK1R-F264^6.51) and a tyrosine in NK2R (NK2R-Y266^6.51), giving r

SUBMITTER: Petersen JE 

PROVIDER: S-EPMC11625327 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature