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

Author

Listed:
  • Yaejin Yun

    (Seoul National University)

  • Hyeongseop Jeong

    (Korea Basic Science Institute)

  • Thibaut Laboute

    (University of Florida
    Imaging Brain & Neuropsychiatry iBraiN U1253)

  • Kirill A. Martemyanov

    (University of Florida)

  • Hyung Ho Lee

    (Seoul National University)

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.

Suggested Citation

  • Yaejin Yun & Hyeongseop Jeong & Thibaut Laboute & Kirill A. Martemyanov & Hyung Ho Lee, 2024. "Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52584-z
    DOI: 10.1038/s41467-024-52584-z
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