RESUMO
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.
Assuntos
Interferon beta/ultraestrutura , Interferon gama/ultraestrutura , Interleucina-5/química , Simulação por Computador , Interferon beta/química , Interferon gama/química , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , SolubilidadeRESUMO
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.
Assuntos
Citocinas/ultraestrutura , Fator Estimulador de Colônias de Granulócitos/ultraestrutura , Hormônio do Crescimento/química , Interferon beta/ultraestrutura , Interferon gama/ultraestrutura , Interleucina-2/química , Interleucina-5/química , Fator Estimulador de Colônias de Macrófagos/ultraestrutura , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
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.
