Movie
Controller
Structure viewers
About EMN Papers
+Search query
-Structure paper
| Title | Cryo-EM structure of the human histamine H receptor/G complex. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 2086, Year 2021 |
| Publish date | Apr 7, 2021 |
 Authors | Ruixue Xia / Na Wang / Zhenmei Xu / Yang Lu / Jing Song / Anqi Zhang / Changyou Guo / Yuanzheng He /  |
| 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. ...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. |
 External links | Nat Commun / PubMed:33828102 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.3 Å |
| Structure data | EMDB-30665, PDB-7dfl: |
| Chemicals |  ChemComp-HSM: |
| Source |
|
 Keywords |  MEMBRANE PROTEIN / complex |
