Powers R, Garrett D S, March C J, Frieden E A, Gronenborn A M, Clore G M
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Science. 1992 Jun 19;256(5064):1673-7. doi: 10.1126/science.256.5064.1673.
The three-dimensional solution structure of recombinant human interleukin-4, a protein of 133 residues and 15.4 kilodaltons that plays a key role in the immune and inflammatory systems, has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is dominated by a left-handed four-helix bundle with an unusual topology comprising two overhand connections. The linker elements between the helices are formed by either long loops, small helical turns, or short strands. The overall topology is remarkably similar to that of growth hormone and granulocyte-macrophage colony stimulating factor, despite the absence of any sequence homology, and substantial differences in the relative lengths of the helices, the length and nature of the various connecting elements, and the pattern of disulfide bridges. These three proteins, however, bind to cell surface receptors belonging to the same hematopoietic superfamily, which suggests that interleukin-4 may interact with its receptor in an analogous manner to that observed in the crystal structure of the growth hormone-extracellular receptor complex.
重组人白细胞介素-4是一种由133个氨基酸残基组成、分子量为15.4千道尔顿的蛋白质，在免疫和炎症系统中起关键作用。其三维溶液结构已通过多维异核磁共振光谱法解析出来。该结构主要由一个左手四螺旋束构成，具有不寻常的拓扑结构，包含两个反手连接。螺旋之间的连接元件由长环、小螺旋转角或短链组成。尽管缺乏任何序列同源性，且螺旋的相对长度、各种连接元件的长度和性质以及二硫键模式存在显著差异，但总体拓扑结构与生长激素和粒细胞-巨噬细胞集落刺激因子的拓扑结构非常相似。然而，这三种蛋白质都与属于同一造血超家族的细胞表面受体结合，这表明白细胞介素-4可能与其受体相互作用的方式类似于在生长激素-细胞外受体复合物晶体结构中观察到的方式。
