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N-甲酰肽fMet-Leu-Phe(fMLP)是来源于细菌的化学趋向性小肽。已知fMIP是活化中性颗粒白细胞的强激活剂,因此阐明fMLP受体(FRP)结合fMLP的结构域对控制炎症的发生、中性白细胞在组织中的浸润具有重要意义。用改进的方法构建了FPR的5个嵌合体及2个突变体,并鉴定了他们结合fMLP的亲和性,取得以下结果:(1)和其他G蛋白偶联性受体不同,FPR的细胞外氨基端结构域(残基1～26)对fMLP结合的重要性不显著。(2)FPR在细胞外的3个环区(loop)对配体的结合是关键性的,其中环区1和环区3尤为重要。(3)FPR的跨膜结构域(TMD)中某些点突变能导致FPR不能和它的配体fMLP充分结合,表明FPR的跨膜结构域也参与对配体的结合。这些结果有助于设计新的FPR颉抗剂。
N-formyl peptide fMet-Leu-Phe (fMLP) is a chemically-derived small peptide derived from bacteria. It is known that fMIP is a potent activator of activated neutrophil leukocytes. Therefore, clarifying the fMLP receptor (FRP) binding domain of fMLP is of great importance in controlling the occurrence of inflammation and infiltration of neutrophils in tissues. Five chimeras and two mutants of FPR were constructed with the improved method and their affinity for fMLP was identified. The following results were obtained: (1) Unlike other G protein-coupled receptors, FPR cells The significance of the extra amino-terminal domain (residues 1-26) to fMLP binding was insignificant. (2) FPR is crucial for ligand binding in 3 extracellular loops, of which loop 1 and loop 3 are especially important. (3) Some point mutations in the transmembrane domain (TMD) of FPR can result in that FPR can not fully bind to its ligand fMLP, indicating that the transmembrane domain of FPR is also involved in ligand binding. These results help to design new FPR antagonists.