Elucidation of the Basic Three-Dimensional Structure of Type I Interferons and Its Functional and Evolutionary Implications

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Abstract
The scientific and personal backgrounds of the crystallographic elucidation of the three-dimensional structure of murine interferon-β(Mu-IFN-β) are described. This structure, elucidated in 1990, is still the only experimentally determined structure for type I IFNs. Model-building studies for various type I IFNs based on the MuIFN-β structure and the arguments on the receptor-binding epitopes appearing since then are reviewed. An updated set of a table and a figure demonstrating a strong correlation between the degree of amino acid sequence variation in various cytokine proteins and that in their cognate receptor proteins is given. The origin of a remarkably larger rate of evolutionary change in amino acid sequences of cytokine proteins despite their physiologic significance is discussed in view of the cytokine network and the neutral theory of evolution.