Structure of formylpeptide receptor 2-Gi complex reveals insights into ligand recognition and signaling

Structure of formylpeptide receptor 2-Gi complex reveals insights into ligand recognition and signaling
Title:
Structure of formylpeptide receptor 2-Gi complex reveals insights into ligand recognition and signaling
Other Titles:
Nature Communications
Publication Date:
14 February 2020
Citation:
Zhuang, Y., Liu, H., Edward Zhou, X. et al. Structure of formylpeptide receptor 2-Gi complex reveals insights into ligand recognition and signaling. Nat Commun 11, 885 (2020). https://doi.org/10.1038/s41467-020-14728-9
Abstract:
Formylpeptide receptors (FPRs) as G protein-coupled receptors (GPCRs) can recognize formylpeptides derived from pathogens or host cells to function in host defense and cell clearance. In addition, FPRs, especially FPR2, can also recognize other ligands with a large chemical diversity generated at different stages of inflammation to either promote or resolve inflammation in order to maintain a balanced inflammatory response. The mechanism underlying promiscuous ligand recognition and activation of FPRs is not clear. Here we report a cryo-EM structure of FPR2-Gi signaling complex with a peptide agonist. The structure reveals a widely open extracellular region with an amphiphilic environment for ligand binding. Together with computational docking and simulation, the structure suggests a molecular basis for the recognition of formylpeptides and a potential mechanism of receptor activation, and reveals conserved and divergent features in Gi coupling. Our results provide a basis for understanding the molecular mechanism of the functional promiscuity of FPRs.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
The data were collected at the David Van Andel Advanced Cryo-EM facility at the Van Andel Research Institute. This work was supported by the National Institutes of Health grants 1R35GM128641 (to C.Z.), 1R01GM127710 (to H.E.X) and 1R01GM130142 (to N.L.), the Van Andel Research Institute funding (to K.M. and H.E.X.), XDB08020303 (to H.E.X.), and funding support from the Biomedical Research Council of A*STAR including the Industry Alignment Fund Pre-Positioning (H18/01/a0/C14) (to H.F. and R.K.V.). Y.Z. acknowledges the support from the UCAS joint Ph.D. Training Program.
Description:
ISSN:
2041-1723
Files uploaded:

File Size Format Action
1106-structure-of-formylpeptide-receptor.pdf 2.88 MB PDF Open