Cryo-EM Structure of Human Class C Orphan GPCR GPR179 Involved in Visual Processing

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Sep 27

PMID 39333506

Authors

Yaejin Yun

Hyeongseop Jeong

Thibaut Laboute

Kirill A Martemyanov

Hyung Ho Lee

Affiliations

Soon will be listed here.

Abstract

GPR179, an orphan class C GPCR, is expressed at the dendritic tips of ON-bipolar cells in the retina. It plays a pivotal role in the initial synaptic transmission of visual signals from photoreceptors, and its deficiency is known to be the cause of complete congenital stationary night blindness. Here, we present the cryo-electron microscopy structure of human GPR179. Notably, the transmembrane domain (TMD) of GPR179 forms a homodimer through the TM1/7 interface with a single inter-protomer disulfide bond, adopting a noncanonical dimerization mode. Furthermore, the TMD dimer exhibits architecture well-suited for the highly curved membrane of the dendritic tip and distinct from the flat membrane arrangement observed in other class C GPCR dimers. Our structure reveals unique structural features of GPR179 TMD, setting it apart from other class C GPCRs. These findings provide a foundation for understanding signal transduction through GPR179 in visual processing and offers insights into the underlying causes of ocular diseases.

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