Structural insights into neurokinin 3 receptor activation by endogenous and analogue peptide agonists.

ABSTRACT: Neurokinin 3 receptor (NK3R) is a tachykinin receptor essential for the hypothalamic-pituitary-gonadal axis. The endogenous peptide agonist neurokinin B (NKB) preferentially activates NK3R, while substance P (SP) binds preferentially to NK1R. In addition, the SP analogue senktide more potently activates NK3R than NKB and SP. However, the mechanisms of preferential binding of peptide and NK3R activation remain elusive. Herein, we determined the cryogenic electron microscopy (cryo-EM) structures of the NK3R-G_q complex bound to NKB, SP and senktide. The three NK3R-G_q/peptide complexes utilize a class of noncanonical receptor activation mechanisms. Combining the structural analysis and functional assay illustrated that the consensus C-termini of the three peptide agonists

SUBMITTER: Sun W 

PROVIDER: S-EPMC10313662 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature