8YUV

Cryo-EM structure of the immepip-bound H3R-Gi complex

This is a non-PDB format compatible entry.

Summary for 8YUV

• Entry DOI: 10.2210/pdb8yuv/pdb
• EMDB information: 39584
• 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, ... (7 entities in total)
• Functional Keywords: gpcr, h3r, histamine receptor, membrane protein/immune system, membrane protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 167661.43

Authors

Shen, Q.,Tang, X.,Wen, X.,Cheng, S.,Xiao, P.,Zang, S.,Shen, D.,Jiang, L.,Zheng, Y.,Zhang, H.,Xu, H.,Mao, C.,Zhang, M.,Hu, W.,Sun, J.,Chen, Z.,Zhang, Y. (deposition date: 2024-03-27, release date: 2024-06-05, Last modification date: 2024-11-06)

Primary citation

Shen, Q.,Tang, X.,Wen, X.,Cheng, S.,Xiao, P.,Zang, S.K.,Shen, D.D.,Jiang, L.,Zheng, Y.,Zhang, H.,Xu, H.,Mao, C.,Zhang, M.,Hu, W.,Sun, J.P.,Zhang, Y.,Chen, Z.
Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs.
Adv Sci, 11:e2310120-e2310120, 2024

PubMed Abstract: G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors HR and HR couple with G- or G-proteins respectively. Here, three cryo-EM structures of HR-G and HR-G complexes are presented at a global resolution of 2.6-2.7 Å. These structures reveal the unique binding pose for endogenous histamine in HR, wherein the amino group interacts with E206 of HR instead of the conserved D114 of other aminergic receptors. Furthermore, comparative analysis of the HR-G and HR-G complexes reveals that the structural geometry of TM5/TM6 determines the primary G-protein selectivity in histamine receptors. Machine learning (ML)-based structuromic profiling and functional analysis of class A GPCR-G-protein complexes illustrate that TM5 length, TM5 tilt, and TM6 outward movement are key determinants of the G and G selectivity among the whole Class A family. Collectively, the findings uncover the common structural geometry within class A GPCRs that determines the primary G- and G-coupling selectivity.

PubMed: 38647423
DOI: 10.1002/advs.202310120

Experimental method

ELECTRON MICROSCOPY (3 Å)