PDBsum entry 6lw5

Membrane protein

PDB id: 6lw5

Contents

Protein chain

427 a.a.

Ligands

TRP-LYS-TYR-MET-VAL-QXV

CLR ×2

Waters ×1

PDB id:

6lw5

Name:

Membrane protein

Title:

Crystal structure of the human formyl peptide receptor 2 in complex with wkymvm

Structure:

Soluble cytochrome b562,n-formyl peptide receptor 2. Chain: a. Synonym: cytochrome b-562,fmlp-related receptor i,fmlp-r-i,formyl peptide receptor-like 1,hm63,lipoxin a4 receptor,lxa4 receptor,rfp. Engineered: yes. Mutation: yes. Trp-lys-tyr-met-val-qxv. Chain: b. Engineered: yes

Source:

Escherichia coli, homo sapiens. Human. Organism_taxid: 562, 9606. Gene: cybc, fpr2, fprh1, fprl1, lxa4r. Expressed in: mammalian expression vector flag-mcs-pcdna3.1. Expression_system_taxid: 2021188. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

2.80Å R-factor: 0.258 R-free: 0.289

Authors:

T.Chen,X.Zong,H.Zhang,M.Wang,Q.Zhao,B.Wu

Key ref:

T.Chen et al. (2020). Structural basis of ligand binding modes at the human formyl peptide receptor 2. Nat Commun, 11, 1208. PubMed id: 32139677 DOI: 10.1038/s41467-020-15009-1

Date:

07-Feb-20 Release date: 25-Mar-20

Protein chain

P0ABE7  (C562_ECOLX) -  Soluble cytochrome b562 from Escherichia coli

Seq: 128 a.a.

Struc: 427 a.a.*

Protein chain

P25090  (FPR2_HUMAN) -  N-formyl peptide receptor 2 from Homo sapiens

Seq: 351 a.a.

Struc: 427 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/s41467-020-15009-1

Nat Commun 11:1208 (2020)

PubMed id: 32139677

Structural basis of ligand binding modes at the human formyl peptide receptor 2.

T.Chen, M.Xiong, X.Zong, Y.Ge, H.Zhang, M.Wang, G.Won Han, C.Yi, L.Ma, R.D.Ye, Y.Xu, Q.Zhao, B.Wu.

ABSTRACT

The human formyl peptide receptor 2 (FPR2) plays a crucial role in host defense and inflammation, and has been considered as a drug target for chronic inflammatory diseases. A variety of peptides with different structures and origins have been characterized as FPR2 ligands. However, the ligand-binding modes of FPR2 remain elusive, thereby limiting the development of potential drugs. Here we report the crystal structure of FPR2 bound to the potent peptide agonist WKYMVm at 2.8 Å resolution. The structure adopts an active conformation and exhibits a deep ligand-binding pocket. Combined with mutagenesis, ligand binding and signaling studies, key interactions between the agonist and FPR2 that govern ligand recognition and receptor activation are identified. Furthermore, molecular docking and functional assays reveal key factors that may define binding affinity and agonist potency of formyl peptides. These findings deepen our understanding about ligand recognition and selectivity mechanisms of the formyl peptide receptor family.