Oritani K, Kincade P W, Zhang C, Tomiyama Y, Matsuzawa Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan.
Cytokine Growth Factor Rev. 2001 Dec;12(4):337-48. doi: 10.1016/s1359-6101(01)00009-0.
The type I interferon (IFN) family includes IFN-alpha, IFN-beta, IFN-pi, and IFN-tau. These molecules are clustered according to sequence homologies, use of the same cell surface receptor, and similar functions. IFN-alpha and IFN-beta have a globular structure composed of five a-helices. Their receptors, IFNAR1 and IFNAR2, belong to the class II cytokine receptor family for a-helical cytokines. Information about structure-function relationships between these and other IFNs is being provided by comparative sequence analysis, reference to a prototypic three-dimensional structure, analysis with monoclonal antibodies, construction of hybrid molecules and site directed mutagenesis. While much remains to be done, it should someday be possible to understand differences among IFNs in terms of how they interact with their corresponding receptors. Our recently identified IFN-like molecule, limitin, has weak sequence homology to IFN-alpha, IFN-beta, and IFN-omega and displays its biological functions through the same IFN-alpha/beta receptors. While limitin has antiproliferative, immunomodulatory, and antiviral effects like IFN-alpha and IFN-beta, it is unique in lacking influence on myeloid and erythroid progenitors. Further analysis of this functionally unique cytokine should be informative about complex IFN-receptor interactions. Furthermore, a human homologue or synthetic variant might be superior for clinical applications as an IFN without myelosuppressive properties.
I型干扰素（IFN）家族包括IFN-α、IFN-β、IFN-π和IFN-τ。这些分子根据序列同源性、使用相同的细胞表面受体以及相似的功能进行聚类。IFN-α和IFN-β具有由五个α螺旋组成的球状结构。它们的受体IFNAR1和IFNAR2属于α螺旋细胞因子的II类细胞因子受体家族。通过比较序列分析、参考原型三维结构、用单克隆抗体进行分析、构建杂交分子和定点诱变，正在提供有关这些干扰素与其他干扰素之间结构-功能关系的信息。虽然还有很多工作要做，但总有一天应该能够从干扰素与相应受体相互作用的方式来理解它们之间的差异。我们最近鉴定出的类干扰素分子limitin与IFN-α、IFN-β和IFN-ω具有较弱的序列同源性，并通过相同的IFN-α/β受体发挥其生物学功能。虽然limitin具有与IFN-α和IFN-β类似的抗增殖、免疫调节和抗病毒作用，但它的独特之处在于对髓系和红系祖细胞没有影响。对这种功能独特的细胞因子的进一步分析应该有助于了解复杂的干扰素-受体相互作用。此外，作为一种没有骨髓抑制特性的干扰素，人同源物或合成变体在临床应用中可能更具优势。
