GPR156
Description
The GPR156 (G protein-coupled receptor 156) is a protein-coding gene located on chromosome 3.
GPR156 (G protein-coupled receptor 156) is a human gene that encodes a G protein-coupled receptor belonging to the metabotropic glutamate receptor subfamily. Initially proposed as a potential GABAB receptor subunit due to sequence homology, it was later found to not respond to GABAB ligands when expressed alone or with other GABAB subunits. In vitro studies revealed GPR156's constitutive activity, displaying high basal activation and coupling with members of the Gi/Go heterotrimeric G protein family. Research in 2021 indicated that GPR156 modulates hair cell orientation in the cochlea, suggesting a potential role in congenital hearing loss. The interaction of GPR156 with any of the Gi/o heterotrimers regulates hair cell orientation. Cryogenic electron microscopy was employed in 2024 to characterize the molecular structures of G-free and Go-bound GPR156.
Structure
GPR156 distinguishes itself from other class C GPCR family members by lacking a large extracellular domain. Structural analyses revealed that the asymmetric binding of Go-protein to GPR156 triggers a conformational change in its cytoplasmic face without altering the dimer interface. While inactive class C GPCRs undergo rearrangement of their dimeric interface, the agonist- and/or positive allosteric modulator-bound class C GPCRs retain their dimeric interface upon G-protein binding.
Orphan receptor, meaning its specific ligand and function are unknown.
GPR156 is also known as DFNB121, GABABL, PGR28.
