ABSTRACT
On the basis of crystallographic data, the alpha-helices of interferon-beta as well as each domain of interferon-gamma are located in two layers. This results in a different contribution from the amino acids placing in the middle and border alpha-helices of the layer to the hydrophobic core of the molecule. A close analysis of the structure of dimeric interleukin-5 shows related arrangements of alpha-helices. The full schemes of the interhelix contacts of interferons-beta, -gamma, and dimeric interleukin-5 were constructed. Schemes for interleukin-5 show that extension of helices correlates with the dimer topology.
Subject(s)
Interferon-beta/ultrastructure , Interferon-gamma/ultrastructure , Interleukin-5/chemistry , Computer Simulation , Interferon-beta/chemistry , Interferon-gamma/chemistry , Protein Conformation , Protein Structure, Secondary , Protein Structure, Tertiary , SolubilityABSTRACT
Schemes of the four-helix bundle surfaces of interleukin-2, -4, -5, granulocyte/macrophage-, granulocyte-, macrophage-colony-stimulating factor, interferon-beta, -gamma and growth hormone were designed. All cytokines appeared to have the structurally similar "holes" on the surfaces. They were suggested to serve as a part of the main receptor-binding sites.
Subject(s)
Cytokines/ultrastructure , Granulocyte Colony-Stimulating Factor/ultrastructure , Growth Hormone/chemistry , Interferon-beta/ultrastructure , Interferon-gamma/ultrastructure , Interleukin-2/chemistry , Interleukin-5/chemistry , Macrophage Colony-Stimulating Factor/ultrastructure , Protein Structure, Secondary , Protein Structure, TertiaryABSTRACT
An atomic coordinate five alpha-helix three-dimensional model is presented for human interferon alpha-2 (HuIFN alpha 2). The HuIFN alpha 2 structure was constructed from murine interferon beta (MuIFN beta) by homology modeling using the STEREO and IMPACT programs. The HuIFN alpha 2 model is consistent with its known biochemical and biophysical properties including epitope mapping. Lysine residues predicted to be buried in the model were primarily unreactive with succinimidyl-7-amino-4-methylcoumarin-3-acetic acid (AMCA-NHS), a lysine modification agent, as shown by mass spectrometric analysis of tryptic digests. N-terminal sequence analysis of polypeptides generated by limited digestion of HuIFN alpha 2 with endoproteinase Lys-C demonstrated rapid cleavage at K31, which is consistent with the presence of this residue in a loop in the proposed HuIFN alpha 2 model. Based on this model structure potential receptor binding sites are identified.
