EMD-32883

Single-particle
2.83 Å
EMD-32883 Deposition: 15/02/2022
Map released: 28/09/2022
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-32883

Protein 110 and 13 complex

EMD-32883

Single-particle
2.83 Å
EMD-32883 Deposition: 15/02/2022
Map released: 28/09/2022
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: GPCR/G-protein complex
Fitted models: 7wy0 (Avg. Q-score: 0.45)

Deposition Authors: He Y , Zhu X
Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling.
Zhu X, Qian Y, Li X, Xu Z, Xia R, Wang N, Liang J, Yin H, Zhang A, Guo C, Wang G, He Y
(2022) Nat Commun , 13 , 5513 - 5513
PUBMED: 36127364
DOI: doi:10.1038/s41467-022-33173-4
ISSN: 2041-1723
Abstract:
Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with Gq, Gs, Gi, G12 and G13. The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G12 and GPCR/G13 engagements. A comparison of Gq, Gs, Gi, G12 and G13 engagements with GPR110 reveals details of G-protein engagement, including a dividing point at the far end of the alpha helix 5 (αH5) of Gα subunit that separates Gq/Gs engagements from Gi/G12/G13 engagements. This is also where Gq/Gs bind the receptor through both hydrophobic and polar interaction, while Gi/G12/G13 engage receptor mainly through hydrophobic interaction. We further provide physiological evidence of GPR110 activation via stalk peptide. Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework for understanding aGPCR activation and GPR110 signaling.