Mott H R, Baines B S, Hall R M, Cooke R M, Driscoll P C, Weir M P, Campbell I D
Glaxo Research & Development Ltd., Medicines Research Centre, Stevenage, Hertfordshire, U.K.
J Mol Biol. 1995 Apr 14;247(5):979-94. doi: 10.1006/jmbi.1994.0194.
Interleukin 2 (IL-2) is one of the major cytokines produced by T lymphocytes in response to antigen. It is a potent growth and differentiation factor for several cell-types and is structurally related to the four-helix bundle family of cytokines. Mutation of residue Phe42 to Ala abolishes binding to the alpha chain of the tri-partite IL-2 receptor. The three-dimensional structure of the F42A mutant IL-2 has been calculated by two dimensional NMR methods and compared to a structure of wild-type IL-2 determined by X-ray crystallography. The overall topology of the two structures is the same. The main differences between the structures are within the ill-defined loops connecting the helices and the region of the protein that is believed to interact with the alpha-chain of the receptor. Thus, the mutation of Phe42 to Ala does not perturb the overall three-dimensional structure of IL-2, and does not appear to change the putative binding sites for the beta and gamma chains of the receptor. The structural differences observed in this mutant suggest that the replacement of Phe42 with Ala causes the re-orientation of neighbouring side-chains that are also involved in binding the alpha-chain of the receptor.
白细胞介素2（IL-2）是T淋巴细胞在对抗抗原时产生的主要细胞因子之一。它是几种细胞类型的强效生长和分化因子，在结构上与细胞因子的四螺旋束家族相关。将第42位残基苯丙氨酸（Phe）突变为丙氨酸（Ala）会消除与三方IL-2受体α链的结合。已通过二维核磁共振方法计算出F42A突变体IL-2的三维结构，并与通过X射线晶体学确定的野生型IL-2结构进行了比较。两种结构的整体拓扑相同。结构之间的主要差异在于连接螺旋的不明确环内以及被认为与受体α链相互作用的蛋白质区域。因此，将Phe42突变为Ala不会扰乱IL-2的整体三维结构，并且似乎不会改变受体β链和γ链的假定结合位点。在该突变体中观察到的结构差异表明，用Ala取代Phe42会导致也参与结合受体α链的相邻侧链重新定向。
