RECEPTOR BINDING DOMAIN OF PEPTIDE AGONISTS

在绘制受体结合图谱方面已经取得了相当大的进展 然而，阳离子生物胺激素的研究进展甚微 对确定G蛋白结合部位性质的几点看法 偶联受体，结合大小从3到3的多肽配体 (FMLP)到数百个残基(黄体生成素和卵泡刺激素)。很明显，所有的G- 然而，蛋白质偶联受体有一些共同的结构特征， 在结合结构域方面也有很大的差异。在……里面 我们选择这一建议来阐明 G蛋白超家族中的白介素8受体 偶联受体。白介素8(IL-8)是一个由72个氨基酸组成的多肽 由许多类型的细胞分泌，以响应促炎刺激，如 白介素1和肿瘤坏死因子。IL-8诱导跨内皮细胞生长 白细胞介素8受体新亚型的迁移性克隆 关于结构相关的多肽的配基结合特异性， 中性粒细胞激活肽2与黑色素瘤生长刺激 活动(MGSA)。我们确定了配体结合的特异性是 由胞外N-末端决定的，以识别 IL-8/受体之间的相互作用。测绘氨基 配体-受体界面上的酸残基将有助于设计 新的IL-8受体拮抗剂将在治疗中产生影响 炎症性疾病。

Considerable progress has been achieved on mapping the receptor binding site of cationic biogenic amine hormones, however, little progress has been made on determining the nature of the binding site of G-protein coupled receptors that bind peptide ligands of sizes that range from three (fMLP) to several hundred residues (LH and FSH). It is clear that all G- protein coupled receptors share some common structural features, however, there are also major differences with regard to the binding domain. In this proposal we choose to elucidate the binding domain of the interleukin-8 receptor which belongs to the superfamily of G-protein coupled receptors. Interleukin-8 (IL-8) is a 72 amino acid peptide secreted by many cell types in response to proinflammatory stimuli such as interleukin-1, and tumor necrosis factor. IL-8 induces transendothelial migration cloning of Interleukin-8 receptor subtypes exhibiting novel ligand binding specificity with regard to structurally related peptides, neutrophil activating peptide 2 (NAP-2) and melanoma growth stimulating activity (MGSA). We determined that the ligand binding specificity is dictated by the extracellular N-terminus to identify the residues at the IL-8/receptor interface by using a genetic approach. Mapping the amino acid residues at the ligand-receptor interface will aid toward the design of novel IL-8 receptor antagonists that will impact in the treatment of inflammatory disorders.