7X10
ADGRL3/miniG12 complex
Summary for 7X10
Entry DOI | 10.2210/pdb7x10/pdb |
EMDB information | 32932 |
Descriptor | engineered G alpha 12 subunit, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (5 entities in total) |
Functional Keywords | gpcr, membrane protein |
Biological source | Homo sapiens More |
Total number of polymer chains | 5 |
Total formula weight | 284055.71 |
Authors | |
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 Gq, Gs, Gi, and G12 coupling. Mol.Cell, 82:4340-4352.e6, 2022 Cited by 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: 36309016DOI: 10.1016/j.molcel.2022.10.009 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (2.93 Å) |
Structure validation
Download full validation report