THE SOLUTION STRUCTURE OF THE F42A MUTANT OF HUMAN INTERLEUKIN-2

Interleukin 2 (IL-2) is one of the major cytokines produced by T lymph ocytes in response to antigen. It is a potent growth and differentiati on factor for several cell-types and is structurally related to the fo ur-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 calc ulated by two dimensional NMR methods and compared to a structure of w ild-type IL-2 determined by X-ray crystallography. The overall topolog y 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 pe rturb the overall three-dimensional structure of IL-2, and does not ap pear to change the putative binding sites for the beta and gamma chain s of the receptor. The structural differences observed in this mutant suggest that the replacement of Phe42 with Ala causes the re-orientati on of neighbouring side-chains that are also involved in binding the a lpha-chain of the receptor.