The structure of human interferon-β:: implications for activity

被引:94
作者
Karpusas, M [1 ]
Whitty, A [1 ]
Runkel, L [1 ]
Hochman, P [1 ]
机构
[1] Biogen Inc, Cambridge, MA 02142 USA
关键词
interferon; crystal structure; cytokine; aggregation; glycosylation; multiple sclerosis;
D O I
10.1007/s000180050248
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interferons (IFNs) are potent extracellular protein mediators of host defence and homoeostasis. This article reviews the structure of human IFN-beta (HuIFN-beta), in particular in relation to its activity. The recently determined crystal structure of HuIFN-beta provides a framework for understanding of the mechanism of differentiation of type I IFNs by their common receptor. Insights are generated by comparison with the structures of other type I IFNs and from the interpretation of existing mutagenesis data. The details of the observed carbohydrate structure, together with biochemical data, implicate the glycosylation of HuIFN-beta, which is uncommon among type I IFNs, as an important factor in the solubility; stability and, consequently, activity of the protein. Finally, these structural implications are discussed in the context of the clinical use of HuIFN-beta.
引用
收藏
页码:1203 / 1216
页数:14
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