Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2

Youwen Zhuang, Lei Wang, Jia Guo, Dapeng Sun, Yue Wang, Weiyi Liu, H. Eric Xu () and Cheng Zhang ()
Additional contact information
Youwen Zhuang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Lei Wang: University of Pittsburgh School of Medicine, University of Pittsburgh
Jia Guo: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Dapeng Sun: University of Pittsburgh School of Medicine, University of Pittsburgh
Yue Wang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Weiyi Liu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
H. Eric Xu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Cheng Zhang: University of Pittsburgh School of Medicine, University of Pittsburgh

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally distinct native peptides and even lipid mediators to either promote or resolve inflammation. Pharmacological targeting of FPRs represents a novel therapeutic approach in treating inflammatory diseases. However, the molecular mechanisms underlying FPR ligand recognition are elusive. We report cryo-EM structures of Gi-coupled FPR1 and FPR2 bound to a formylpeptide and Gi-coupled FPR2 bound to two synthetic peptide and small-molecule agonists. Together with mutagenesis data, our structures reveal the molecular mechanism of formylpeptide recognition by FPRs and structural variations of FPR1 and FPR2 leading to their different ligand preferences. Structural analysis also suggests that diverse FPR agonists sample a conserved activation chamber at the bottom of ligand-binding pockets to activate FPRs. Our results provide a basis for rational drug design on FPRs.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28586-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28586-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28586-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().