7WYB

ADGRL3/Gi complex

Summary for 7WYB

• Entry DOI: 10.2210/pdb7wyb/pdb
• EMDB information: 32890
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (5 entities in total)
• Functional Keywords: gpcr, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 284512.61

Authors

He, Y.,Qian, Y. (deposition date: 2022-02-15, release date: 2022-10-26, Last modification date: 2022-11-30)

Primary citation

Qian, Y.,Ma, Z.,Liu, C.,Li, X.,Zhu, X.,Wang, N.,Xu, Z.,Xia, R.,Liang, J.,Duan, Y.,Yin, H.,Xiong, Y.,Zhang, A.,Guo, C.,Chen, Z.,Huang, Z.,He, Y.
Structural insights into adhesion GPCR ADGRL3 activation and G q , G s , G i , and G 12 coupling.
Mol.Cell, 82:4340-4352.e6, 2022

PubMed Abstract: Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies. A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding pocket of receptors; however, the detailed mechanism remains obscure. Here, we present cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with G, G, G, and G. The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms of aGPCR activation. The structures also reveal the uncharted structural information of GPCR/G coupling. A comparison of G, G, G, and G engagements with ADGRL3 reveals the key determinant of G-protein coupling on the far end of αH5 of Gα. A detailed analysis of the engagements allows us to design mutations that specifically enhance one pathway over others. Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling selectivity.

PubMed: 36309016
DOI: 10.1016/j.molcel.2022.10.009

Experimental method

ELECTRON MICROSCOPY (2.97 Å)