Cryo-EM structure of the human histamine H1 receptor/Gq complex. 2021

Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
Laboratory of Receptor Structure and Signaling, The HIT Center for Life Sciences, Harbin Institute of Technology, Harbin, China.

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 H1R in complex with a Gq 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 Gq engagement in a model of "squash to activate and expand to deactivate". The structure also reveals features for Gq coupling, including the interaction between intracellular loop 2 (ICL2) and the αN-β junction of Gq/11 protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011968 Receptors, Histamine Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action. Histamine Binding Sites,Histamine Receptors,Histamine Receptor,Binding Sites, Histamine,Receptor, Histamine,Sites, Histamine Binding
D011969 Receptors, Histamine H1 A class of histamine receptors discriminated by their pharmacology and mode of action. Most histamine H1 receptors operate through the inositol phosphate/diacylglycerol second messenger system. Among the many responses mediated by these receptors are smooth muscle contraction, increased vascular permeability, hormone release, and cerebral glyconeogenesis. (From Biochem Soc Trans 1992 Feb;20(1):122-5) H1 Receptor,Histamine H1 Receptors,H1 Receptors,Histamine H1 Receptor,Receptors, H1,H1 Receptor, Histamine,H1 Receptors, Histamine,Receptor, H1,Receptor, Histamine H1
D006632 Histamine An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072417 Protein Domains Discrete protein structural units that may fold independently of the rest of the protein and have their own functions. Peptide Domain,Protein Domain,Domain, Peptide,Domain, Protein,Domains, Peptide,Domains, Protein,Peptide Domains
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D043802 GTP-Binding Protein alpha Subunits, Gq-G11 A family of heterotrimeric GTP-binding protein alpha subunits that activate TYPE C PHOSPHOLIPASES dependent signaling pathways. The Gq-G11 part of the name is also spelled Gq/G11. G alpha q Protein,G-Protein, Gq,G-Protein, Gq alpha Family,G-Protein, Gq-G11 alpha Family,G alpha Protein q,G alpha11 Protein,G-Protein, G11,G-Protein, Gq-G11,GTP-Binding Protein alpha Subunit, G11,GTP-Binding Protein alpha Subunit, Gq,Galpha11 Protein,Galphaq Protein,Gq Protein,Gq-G11 G-Protein Family,Gq-G11 G-Proteins,Family, Gq-G11 G-Protein,G Protein, G11,G Protein, Gq,G Protein, Gq G11,G Protein, Gq G11 alpha Family,G Protein, Gq alpha Family,G-Protein Family, Gq-G11,G-Proteins, Gq-G11,G11 G-Protein,GTP Binding Protein alpha Subunit, G11,GTP Binding Protein alpha Subunit, Gq,GTP Binding Protein alpha Subunits, Gq G11,Gq G-Protein,Gq G11 G Protein Family,Gq G11 G Proteins,Gq-G11 G-Protein,Protein, G alpha11,Protein, Galpha11,alpha11 Protein, G
D019204 GTP-Binding Proteins Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-. G-Proteins,GTP-Regulatory Proteins,Guanine Nucleotide Regulatory Proteins,G-Protein,GTP-Binding Protein,GTP-Regulatory Protein,Guanine Nucleotide Coupling Protein,G Protein,G Proteins,GTP Binding Protein,GTP Binding Proteins,GTP Regulatory Protein,GTP Regulatory Proteins,Protein, GTP-Binding,Protein, GTP-Regulatory,Proteins, GTP-Binding,Proteins, GTP-Regulatory

Related Publications

Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
February 2022, Nature communications,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
February 2024, Nature communications,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
March 2019, Nature communications,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
June 2011, Nature,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
November 2018, Cell research,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
August 2021, Nature reviews. Nephrology,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
December 2022, Science advances,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
February 2020, Cell,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
February 2018, Cell research,
Ruixue Xia, and Na Wang, and Zhenmei Xu, and Yang Lu, and Jing Song, and Anqi Zhang, and Changyou Guo, and Yuanzheng He
May 2018, Cell research,
Copied contents to your clipboard!