Steve Ealick's Research Group
Recombinant Human Interleukin-4
PDB file: 2INT
Recombinant human interleukin 4 (rhuIL-4) is a lymphokine that co-stimulates the proliferation of activated B- and T-cells, enhances the production of specific immunoglobulin suclsses, augments the cytotoxic activity of lymphocytes and monocytes and enhances the functional activity of myeloid cells. The protein sequence contains 129 amino acids, including two possible sites for N-linked glycosylation. RhuIL-4 has 6 cystein residues, which form three disulfide bonds. We initially determined the crystal structure of rhuIL-4) at 3.5 Å. resolution by multiple isomorphous replacement techniques and subsequently refined to a resolution of 2.35 Å. by simulated annealing. The final crystallographic R-factor, based on all data in the range 6.0-2.35 Å. (7470 reflections), is 0.232. Bond lengths and bond angles in the molecule have root mean square deviations from ideal values of 0.016 Å. and 2.4°, respectively.
The overall structure is highly compact and globular with a predominantly hydrophobic core. The main structural feature of rhuIL-4 is a four α-helix bundle, which composes approximately 58% of the structure. The helices are arranged in a left-handed antiparallel bundle with two overhand connections. Within these connections is a two-stranded antiparallel β-sheet. Both the tertiary and secondary structures of rhuIL-4 are similar to those of human granulocyte-macrophage colony-stimulating factor.
Walter MR, Cook WJ, Zhao BG. Cameron RP, Jr., Ealick SE, Watler RL, Jr., Reichert P, Nagabhushan TL, Trotta PP and Bugg CE. Crystal Structure of Recombinant Human Interleukin-4. J. Biol. Chem. 267:20371-20376 (1992).
Cook WJ, Ealick SE, Reichert P, Le HV, Nagabhushan TL, Trotta PP, Bugg CE. Crystallization and Preliminary X-ray Investigation of Recombinant Human Interleukin-4. J. Mol. Biol., 218:675-678 (1991).