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

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 1998年 / 54卷 / 11期

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

页码：1203 / 1216

页数：14

共 72 条

[1]

AbdulAhad AK, 1997, CYTOKINES CELL MOL T, V3, P27

[2]

ABRAMOVITCH C, 1994, EMBO J, V13, P5817

[3] NATURAL HUMAN INTERFERON-ALPHA-2 IS O-GLYCOSYLATED [J].

ADOLF, GR ;

KALSNER, I ;

AHORN, H ;

MAURERFOGY, I ;

CANTELL, K .

BIOCHEMICAL JOURNAL, 1991, 276 :511-518

[4] Pharmacokinetics and pharmacodynamics of interferon beta-1a (IFN beta-1a) in healthy volunteers after intravenous, subcutaneous or intramuscular administration [J].

Alam, J ;

McAllister, A ;

Scaramucci, J ;

Jones, W ;

Rogge, M .

CLINICAL DRUG INVESTIGATION, 1997, 14 (01) :35-43

[5]

[Anonymous], INTERFERON SYSTEM

[6]

Antonelli G, 1997, J INTERF CYTOK RES, V17, pS39

[7] THE INTERFERONS - MECHANISMS OF ACTION AND CLINICAL-APPLICATIONS [J].

BARON, S ;

TYRING, SK ;

FLEISCHMANN, WR ;

COPPENHAVER, DH ;

NIESEL, DW ;

KLIMPEL, GR ;

STANTON, GJ ;

HUGHES, TK .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1991, 266 (10) :1375-1383

[8] STRUCTURAL DESIGN AND MOLECULAR EVOLUTION OF A CYTOKINE RECEPTOR SUPERFAMILY [J].

BAZAN, JF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (18) :6934-6938

[9]

Bazer FW, 1997, AM J REPROD IMMUNOL, V37, P412

[10]

BENOIT P, 1993, J IMMUNOL, V150, P707

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