Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Center for Research Equipment, Korea Basic Science Institute, Chungcheongbuk-do, 28119, Republic of Korea.
Nat Commun. 2024 Sep 27;15(1):8299. doi: 10.1038/s41467-024-52584-z.
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.
GPR179 是孤儿类 C GPCR，在视网膜的 ON-双极细胞的树突末梢表达。它在光感受器的视觉信号的初始突触传递中起着关键作用，其缺乏已知是完全先天性静止性夜盲症的原因。在这里，我们呈现了人类 GPR179 的冷冻电镜结构。值得注意的是，GPR179 的跨膜域（TMD）通过 TM1/7 界面形成同源二聚体，具有单个的蛋白内二硫键，采用非典型的二聚化模式。此外，TMD 二聚体表现出非常适合树突末梢高度弯曲的膜的结构，与在其他类 C GPCR 二聚体中观察到的平面膜排列明显不同。我们的结构揭示了 GPR179 TMD 的独特结构特征，使其与其他类 C GPCR 区分开来。这些发现为理解 GPR179 在视觉处理中的信号转导提供了基础，并为眼部疾病的潜在原因提供了深入了解。
