title: Identification of the tethered peptide agonist of the adhesion G protein-coupled receptor GPR64/ADGRG2.
abstract: The epididymis-specific adhesion G protein-coupled receptor (aGPCR) GPR64/ADGRG2 has been shown to be a key-player in the male reproductive system. As its disruption leads to infertility, GPR64 has drawn attention as potential target for male fertility control or improvement. Like the majority of aGPCRs GPR64 is an orphan receptor regarding its endogenous agonist and signal transduction. In this study we examined the G protein-coupling abilities of GPR64 and showed that it is activated through a tethered agonist sequence, which we have previously identified as the Stachel sequence. Synthetic peptides derived from the Stachel region can activate the receptor, opening for the first time the possibility to externally manipulate the receptor activity.
authors.affiliation: Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Lilian M
authors.initials: LM
authors.lastname: Demberg
authors.affiliation: Core Unit Peptide Technologies, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Rothemund
authors.affiliation: Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Schöneberg
authors.affiliation: Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany. Electronic address: ines.liebscher@medizin.uni-leipzig.de.
authors.forename: Ines
authors.initials: I
authors.lastname: Liebscher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004822:Epididymis / Q000378:metabolism; D005298:Fertility / Q000502:physiology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: C492742:Adgrg2 protein, mouse; D009842:Oligopeptides; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins
keywords: G protein; GPCR; GPR64; Molecular pharmacology; Peptide agonist; Signal transduction