8YK0

Cryo-EM structure of human GPR156-Gi3 complex

Summary for 8YK0

• Entry DOI: 10.2210/pdb8yk0/pdb
• EMDB information: 39345 39356
• Descriptor: Probable G-protein coupled receptor 156, 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, ... (7 entities in total)
• Functional Keywords: gpcr, class c, gpr156, cryo-em, homodimer, active state, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 158808.54

Authors

Ma, X.Y.,Chen, L.N.,Liao, M.H.,Zhang, L.Y.,Xi, K.,Guo, J.M. (deposition date: 2024-03-03, release date: 2025-02-05)

Primary citation

Ma, X.,Chen, L.N.,Liao, M.,Zhang, L.,Xi, K.,Guo, J.,Shen, C.,Shen, D.D.,Cai, P.,Shen, Q.,Qi, J.,Zhang, H.,Zang, S.K.,Dong, Y.J.,Miao, L.,Qin, J.,Ji, S.Y.,Li, Y.,Liu, J.,Mao, C.,Zhang, Y.,Chai, R.
Molecular insights into the activation mechanism of GPR156 in maintaining auditory function.
Nat Commun, 15:10601-10601, 2024

PubMed Abstract: The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through G. Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156-G complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus. The GPR156 dimer in both apo state and G protein-coupled state adopt a transmembrane (TM)5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. Furthermore, C-terminus in G-bound subunit of GPR156 plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. Together, these results explain how GPR156 constitutive activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function.

PubMed: 39638804
DOI: 10.1038/s41467-024-54681-5

Experimental method

ELECTRON MICROSCOPY (2.4 Å)