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-Structure paper
Title | Cryo-EM structure of the human histamine H receptor/G complex. |
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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 |
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Keywords | MEMBRANE PROTEIN / complex |