7DFL

Cryo-EM structure of histamine H1 receptor Gq complex

Summary for 7DFL

• Entry DOI: 10.2210/pdb7dfl/pdb
• EMDB information: 30665
• Descriptor: Histamine H1 receptor, 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, ... (6 entities in total)
• Functional Keywords: complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 167398.60

Authors

He, Y.,Xia, R.,Wang, N.,Xu, Z. (deposition date: 2020-11-09, release date: 2021-03-31, Last modification date: 2024-11-20)

Primary citation

Xia, R.,Wang, N.,Xu, Z.,Lu, Y.,Song, J.,Zhang, A.,Guo, C.,He, Y.
Cryo-EM structure of the human histamine H 1 receptor/G q complex.
Nat Commun, 12:2086-2086, 2021

PubMed Abstract: Histamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human HR in complex with a G protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for G engagement in a model of "squash to activate and expand to deactivate". The structure also reveals features for G coupling, including the interaction between intracellular loop 2 (ICL2) and the αN-β junction of G protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines.

PubMed: 33828102
DOI: 10.1038/s41467-021-22427-2

Experimental method

ELECTRON MICROSCOPY (3.3 Å)