8XYD
Structure of Platelet-activating factor receptor-G protein complex bound to platelet-activating factor
Summary for 8XYD
| Entry DOI | 10.2210/pdb8xyd/pdb |
| EMDB information | 38769 |
| Descriptor | Platelet-activating factor receptor, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total) |
| Functional Keywords | gpcr, ptafr, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 151705.17 |
| Authors | Fan, W.,Xu, Y.,Zhuang, Y.,Xu, H.E. (deposition date: 2024-01-19, release date: 2024-11-13, Last modification date: 2024-11-27) |
| Primary citation | Fan, W.,Xu, Y.,He, X.,Luo, P.,Zhu, J.,Li, J.,Wang, R.,Yuan, Q.,Wu, K.,Hu, W.,Zhao, Y.,Xu, S.,Cheng, X.,Wang, Y.,Xu, H.E.,Zhuang, Y. Molecular basis for the activation of PAF receptor by PAF. Cell Rep, 43:114422-114422, 2024 Cited by PubMed Abstract: Platelet-activating factor (PAF) is a potent phospholipid mediator crucial in multiple inflammatory and immune responses through binding and activating the PAF receptor (PAFR). However, drug development targeting the PAFR has been limited, partly due to an incomplete understanding of its activation mechanism. Here, we present a 2.9-Å structure of the PAF-bound PAFR-G complex. Structural and mutagenesis analyses unveil a specific binding mode of PAF, with the choline head forming cation-π interactions within PAFR hydrophobic pocket, while the alkyl tail penetrates deeply into an aromatic cleft between TM4 and TM5. Binding of PAF modulates conformational changes in key motifs of PAFR, triggering the outward movement of TM6, TM7, and helix 8 for G protein coupling. Molecular dynamics simulation suggests a membrane-side pathway for PAF entry into PAFR via the TM4-TM5 cavity. By providing molecular insights into PAFR signaling, this work contributes a foundation for developing therapeutic interventions targeting PAF signal axis. PubMed: 38943642DOI: 10.1016/j.celrep.2024.114422 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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