Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing

Area of Science:

• Structural biology
• Neuroscience
• Ophthalmology

Background:

• GPR179 is an orphan class C GPCR located at the dendritic tips of retinal ON-bipolar cells.
• It is essential for initial visual signal transmission from photoreceptors.
• GPR179 deficiency causes complete congenital stationary night blindness.

Purpose of the Study:

• To determine the cryo-electron microscopy structure of human GPR179.
• To elucidate the unique structural features and dimerization mode of GPR179.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the structure of human GPR179.
• Analysis focused on the transmembrane domain (TMD) and its dimerization.

Main Results:

• The transmembrane domain (TMD) of GPR179 forms a homodimer via the TM1/7 interface with a unique inter-protomer disulfide bond.
• This noncanonical dimerization mode results in an architecture suited for the curved membrane of dendritic tips, differing from other class C GPCRs.
• Unique structural features of the GPR179 TMD were identified.

Conclusions:

• The determined structure provides a foundation for understanding GPR179's role in visual signal transduction.
• These insights can illuminate the molecular basis of congenital stationary night blindness and other ocular diseases.