Crystal structure of human recombinant interleukin‐4 at 2.25 Å resolution

The crystal structure of human recombinant interleukin‐4 (IL‐4) has been solved by multiple isomorphous replacement, and refined to an R factor of 0.218 at 2.25 Å resolution. The molecule is a left‐handed four‐helix bundle with a short stretch of β sheet. The structure bears close resemblance to other cytokines such as granulocyte‐macrophage colony stimulating factor (GM‐CSF). Although no sequence similarity of IL‐4 to GM‐CSF and other related cytokines has been previously postulated, structure‐based alignment of IL‐4 and GM‐CSF revealed that the core of the molecules, including large parts of all four helices and extending over half of the molecule, has 30% sequence identity. This may have identified regions which are not only important to maintain structure, but could also play a role in receptor binding.

[1]  R A Smith,et al.  Human interleukin 4. The solution structure of a four-helix bundle protein. , 1992, Journal of molecular biology.

[2]  Scott R. Presnell,et al.  Experimental and theoretical studies of the three‐dimensional structure of human interleukin‐4 , 1991, Proteins.

[3]  S. Rosenberg,et al.  Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma , 1988, The Journal of experimental medicine.

[4]  K. Hodgson,et al.  Crystallization and crystal data of monellin. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C. Bugg,et al.  Crystallization and preliminary X-ray investigation of recombinant human interleukin 4. , 1991, Journal of molecular biology.

[6]  Rapid preparation of proteins for crystallization trials. , 1989, BioTechniques.

[7]  Barry C. Finzel,et al.  The use of an imaging proportional counter in macromolecular crystallography , 1987 .

[8]  W. Hendrickson Stereochemically restrained refinement of macromolecular structures. , 1985, Methods in enzymology.

[9]  S. Leach,et al.  Conformational homologies among cytokines: Interleukins and colony stimulating factors , 1988, Journal of molecular recognition : JMR.

[10]  B. Violand,et al.  Three-dimensional structure of a genetically engineered variant of porcine growth hormone. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[11]  K. Diederichs,et al.  Novel fold and putative receptor binding site of granulocyte-macrophage colony-stimulating factor. , 1991, Science.

[12]  A. Gronenborn,et al.  Crystal structure of interleukin 8: symbiosis of NMR and crystallography. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[13]  K. Arai,et al.  Molecular Biology of Interleukin 4 and Interleukin 5 Genes and Biology of their Products that Stimulate B Cells, T Cells and Hemopoietic Cells , 1988, Immunological reviews.

[14]  Jones Ta,et al.  Diffraction methods for biological macromolecules. Interactive computer graphics: FRODO. , 1985, Methods in enzymology.

[15]  D. S. Garrett,et al.  Determination of the secondary structure and folding topology of human interleukin-4 using three-dimensional heteronuclear magnetic resonance spectroscopy. , 1992, Biochemistry.

[16]  C. Dobson,et al.  Secondary structure and topology of human interleukin 4 in solution. , 1991, Biochemistry.

[17]  D. S. Garrett,et al.  Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy. , 1993, Science.

[18]  J. Bazan,et al.  Structural design and molecular evolution of a cytokine receptor superfamily. , 1990, Proceedings of the National Academy of Sciences of the United States of America.