Structural and molecular dynamics insights into the competitive inhibition of the platelet-activating factor receptor by acyl-PAF.

ABSTRACT: Platelet-activating factor (PAF) promotes cellular activation, inflammation, and platelet aggregation, leading to acute thrombosis. The remodeling pathway swiftly produces PAF upon activation, establishing intracellular signaling via the PAF receptor (PAFR). Alkyl-PAF exhibits the aforementioned inflammatory properties; conversely, its structural analog acyl-PAF elicits a diminished response and functions as an endogenous PAFR antagonist. The underlying mechanism remains undefined. We conducted the molecular dynamics simulation to elucidate the interactions of acyl-PAF or alkyl-PAF on PAFR. Results showed that alkyl-PAF and acyl-PAF share the same binding pocket. However, acyl-PAF increases the radius of gyration and root-mean-square deviation of PAFR, resulting in structural instability.

SUBMITTER: Hung SC 

PROVIDER: S-EPMC12648956 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature