A Tethered Agonist within the Ectodomain Activates the Adhesion G Protein-Coupled Receptors GPR126 and GPR133 | Zendy

Ines Liebscher | Zendy; Julia Schön | Zendy; Sarah C. Petersen | Zendy; Liane Fischer | Zendy; Nina Auerbach | Zendy; Lilian Marie Demberg | Zendy; Amit Mogha | Zendy; Maxi Cöster | Zendy; Kay-Uwe Simon | Zendy; Sven Rothemund | Zendy; Kelly R. Monk | Zendy; Torsten Schöneberg | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

A Tethered Agonist within the Ectodomain Activates the Adhesion G Protein-Coupled Receptors GPR126 and GPR133

Author(s) -

Ines Liebscher,

Julia Schön,

Sarah C. Petersen,

Liane Fischer,

Nina Auerbach,

Lilian Marie Demberg,

Amit Mogha,

Maxi Cöster,

Kay-Uwe Simon,

Sven Rothemund,

Kelly R. Monk,

Torsten Schöneberg

Publication year - 2014

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2014.11.036

Subject(s) - ectodomain , g protein coupled receptor , agonist , receptor , microbiology and biotechnology , transmembrane protein , signal transduction , biology , transmembrane domain , zebrafish , chemistry , biochemistry , gene

Adhesion G protein-coupled receptors (aGPCRs) comprise the second largest yet least studied class of the GPCR superfamily. aGPCRs are involved in many developmental processes and immune and synaptic functions, but the mode of their signal transduction is unclear. Here, we show that a short peptide sequence (termed the Stachel sequence) within the ectodomain of two aGPCRs (GPR126 and GPR133) functions as a tethered agonist. Upon structural changes within the receptor ectodomain, this intramolecular agonist is exposed to the seven-transmembrane helix domain, which triggers G protein activation. Our studies show high specificity of a given Stachel sequence for its receptor. Finally, the function of Gpr126 is abrogated in zebrafish with a mutated Stachel sequence, and signaling is restored in hypomorphic gpr126 zebrafish mutants upon exogenous Stachel peptide application. These findings illuminate a mode of aGPCR activation and may prompt the development of specific ligands for this currently untargeted GPCR family.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research