Beall C J, Mahajan S, Kolattukudy P E
Biotechnology Center, Ohio State University, Columbus 43210.
J Biol Chem. 1992 Feb 15;267(5):3455-9.
The small cytokine monocyte chemoattractant protein-1 has structural similarity to the neutrophil chemoattractant interleukin-8, but each protein is specific in attracting its own target cell. To investigate the structural basis of this cell type specificity, we have developed an Escherichia coli expression system for the monocyte chemoattractant and mutagenized selected amino acid residues to ones found at the corresponding positions of interleukin-8. We find that a double mutation of tyrosine 28 and arginine 30 to leucine and valine, respectively, causes a drastic decrease in chemotactic activity toward monocytes with the appearance of a novel (interleukin-8-like) neutrophil chemotactic activity. Computer graphic analysis predicts that, with the double substitution, a putative receptor binding groove of the monocyte chemoattractant protein would become topographically similar to that of interleukin-8. We therefore postulate that one or both of these amino acid residues are part of the binding contact of these small cytokines and their receptors.
小细胞因子单核细胞趋化蛋白-1与中性粒细胞趋化因子白细胞介素-8在结构上有相似性，但每种蛋白质在吸引自身靶细胞方面具有特异性。为了研究这种细胞类型特异性的结构基础，我们开发了一种用于单核细胞趋化因子的大肠杆菌表达系统，并将选定的氨基酸残基突变为在白细胞介素-8相应位置发现的氨基酸残基。我们发现，分别将酪氨酸28和精氨酸30双突变为亮氨酸和缬氨酸，会导致对单核细胞的趋化活性急剧下降，并出现新的（白细胞介素-8样）中性粒细胞趋化活性。计算机图形分析预测，通过双重替换，单核细胞趋化蛋白的假定受体结合槽在拓扑结构上将变得与白细胞介素-8相似。因此，我们推测这些氨基酸残基中的一个或两个是这些小细胞因子与其受体结合接触的一部分。
