Labriola-Tompkins E, Chandran C, Varnell T A, Madison V S, Ju G
Department of Inflammation/Autoimmune Diseases, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Protein Eng. 1993 Jul;6(5):535-9. doi: 10.1093/protein/6.5.535.
Using oligonucleotide-directed mutagenesis, the binding site on human interleukin-1 alpha (IL-1 alpha) for the human type I IL-1 receptor (IL-1R) has been analyzed. Substitution of seven amino acids (Arg12, Ile14, Asp60, Asp61, Ile64, Lys96 and Trp109) resulted in a significant loss of binding to the receptor. Based on crystallographic information, the side chains of these residues are clustered in one region of IL-1 alpha and exposed on the surface of the protein. Five of the residues in the IL-1 alpha binding site align with the binding residues previously determined in human IL-1 beta, demonstrating that the type I IL-1R recognizes homologous regions in both ligands. Unexpectedly, only three of the aligned residues are identical between IL-1 alpha and IL-1 beta. These observations suggest that the composition of contact residues in the binding site is unique for each ligand-receptor complex in the IL-1 system.
利用寡核苷酸定向诱变技术，对人白细胞介素-1α（IL-1α）与人Ⅰ型白细胞介素-1受体（IL-1R）的结合位点进行了分析。七个氨基酸（Arg12、Ile14、Asp60、Asp61、Ile64、Lys96和Trp109）的替换导致与受体的结合显著丧失。基于晶体学信息，这些残基的侧链聚集在IL-1α的一个区域并暴露在蛋白质表面。IL-1α结合位点中的五个残基与先前在人IL-1β中确定的结合残基对齐，表明Ⅰ型IL-1R识别两种配体中的同源区域。出乎意料的是，IL-1α和IL-1β之间只有三个对齐的残基是相同的。这些观察结果表明，结合位点中接触残基的组成对于IL-1系统中的每个配体-受体复合物都是独特的。
