7dfl

From Proteopedia

Jump to: navigation, search

Cryo-EM structure of histamine H1 receptor Gq complex

Structural highlights

7dfl is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.3Å
Ligands:HSM
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HRH1_HUMAN In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.

Publication Abstract from PubMed

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 H(1)R in complex with a G(q) 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(q) engagement in a model of "squash to activate and expand to deactivate". The structure also reveals features for G(q) coupling, including the interaction between intracellular loop 2 (ICL2) and the alphaN-beta junction of G(q/11) protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines.

Cryo-EM structure of the human histamine H(1) receptor/G(q) complex.,Xia R, Wang N, Xu Z, Lu Y, Song J, Zhang A, Guo C, He Y Nat Commun. 2021 Apr 7;12(1):2086. doi: 10.1038/s41467-021-22427-2. PMID:33828102[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
9 reviews cite this structure
Shulpekova et al. (2021)
No citations found

See Also

References

  1. 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. 2021 Apr 7;12(1):2086. PMID:33828102 doi:10.1038/s41467-021-22427-2

Contents


PDB ID 7dfl

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools