PDBsum entry 5zkq

Signaling protein

PDB id: 5zkq

Contents

Protein chains

279 a.a.

399 a.a.

Ligands

9EU ×2

OLC ×7

SO4 ×6

Metals

_ZN ×2

Waters ×2

PDB id:

5zkq

Name:

Signaling protein

Title:

Crystal structure of the human platelet-activating factor receptor in complex with abt-491

Structure:

Platelet-activating factor receptor,endolysin,endolysin, platelet-activating factor receptor. Chain: a, b. Synonym: pafr, lysis protein, lysozyme, muramidase. Engineered: yes. Mutation: yes

Source:

Homo sapiens, enterobacteria phage t4. Human, bacteriophage t4. Organism_taxid: 9606, 10665. Gene: ptafr, pafr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.90Å R-factor: 0.204 R-free: 0.235

Authors:

C.Cao,Q.Zhao,X.C.Zhang,B.Wu

Key ref:

C.Cao et al. (2018). Structural basis for signal recognition and transduction by platelet-activating-factor receptor. Nat Struct Mol Biol, 25, 488-495. PubMed id: 29808000 DOI: 10.1038/s41594-018-0068-y

Date:

25-Mar-18 Release date: 20-Jun-18

Protein chain

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 279 a.a.*

Protein chain

P25105  (PTAFR_HUMAN) -  Platelet-activating factor receptor from Homo sapiens

Seq: 342 a.a.

Struc: 279 a.a.*

Protein chain

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 399 a.a.*

Protein chain

P25105  (PTAFR_HUMAN) -  Platelet-activating factor receptor from Homo sapiens

Seq: 342 a.a.

Struc: 399 a.a.*

* PDB and UniProt seqs differ at 334 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

DOI no: 10.1038/s41594-018-0068-y

Nat Struct Mol Biol 25:488-495 (2018)

PubMed id: 29808000

Structural basis for signal recognition and transduction by platelet-activating-factor receptor.

C.Cao, Q.Tan, C.Xu, L.He, L.Yang, Y.Zhou, Y.Zhou, A.Qiao, M.Lu, C.Yi, G.W.Han, X.Wang, X.Li, H.Yang, Z.Rao, H.Jiang, Y.Zhao, J.Liu, R.C.Stevens, Q.Zhao, X.C.Zhang, B.Wu.

ABSTRACT

Platelet-activating-factor receptor (PAFR) responds to platelet-activating factor (PAF), a phospholipid mediator of cell-to-cell communication that exhibits diverse physiological effects. PAFR is considered an important drug target for treating asthma, inflammation and cardiovascular diseases. Here we report crystal structures of human PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491 at 2.8-Å and 2.9-Å resolution, respectively. The structures, supported by molecular docking of PAF, provide insights into the signal-recognition mechanisms of PAFR. The PAFR-SR 27417 structure reveals an unusual conformation showing that the intracellular tips of helices II and IV shift outward by 13 Å and 4 Å, respectively, and helix VIII adopts an inward conformation. The PAFR structures, combined with single-molecule FRET and cell-based functional assays, suggest that the conformational change in the helical bundle is ligand dependent and plays a critical role in PAFR activation, thus greatly extending knowledge about signaling by G-protein-coupled receptors.