Structure/function studies of murine interferon-α1 using site-directed mutagenesis followed by in vitro synthesis

Lai, May C.; Beilharz, Manfred W.; Scalzo, Anthony A.; Garrett, Kerryn L.; Cannon, James F.; Boyer, S.J.; Swaminathan, Nalini

doi:10.1016/0166-3542(92)90006-q

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…Her conclusion is in almost perfect agreement with that presented in our previous review/13' In a series of site-directed mutagenesis studies on Mu-IFN-al using murine cells as tar¬ gets, Lai et al/26' confirmed the functional significance of loop AB and loop DE but expressed difficulty in correlating their positive (affecting antiviral activity) results on several amino acid residues on helix C with our previous identification of the hot segments. In a structure-function study of the region (residues [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] corresponding to loop AB (N-terminal and middle portions) in Hu-IFN-a4, Waine et al/27' noted the func¬ tional importance of Leu 30, Arg 33, and Phe 36. As clearly recognized after the final refinement of the Mu-IFN-ß struc¬ ture/16' the side chains of Leu 30 (30) and Phe 36 (36) play important roles as spacers between loop AB and the core of the molecule, whereas that of Arg 33 (33) protrudes into the sol¬ vent.…”

Section: Ifn-/3 Crystal Structurementioning

confidence: 99%

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

Mitsui¹,

Senda²

1997

Journal of Interferon & Cytokine Research

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The scientific and personal backgrounds of the crystallographic elucidation of the three-dimensional structure of murine interferon-beta (Mu-IFN-beta) 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 Mu-IFN-beta 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.

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Section: Ifn-/3 Crystal Structurementioning

confidence: 99%

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

Mitsui¹,

Senda²

1997

Journal of Interferon & Cytokine Research

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Synergistic role of type I interferons in the induction of protective cytotoxic T lymphocytes

Hoegen

1995

Immunology Letters

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Low-Dose Oral Type I Interferons Reduce Early Virus Replication of Murine CytomegalovirusIn Vivo

Beilharz¹,

McDonald²,

Watson³

et al. 1997

Journal of Interferon & Cytokine Research

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Immunity to viral infections involves both innate and antigen-specific immune responses. The antiviral properties of interferons (IFNs) are part of the innate immune response. Low doses of type I IFNs (IFN-alpha and IFN-beta) administered daily (10 IU per mouse) by the oral route significantly reduced the early replication of murine cytomegalovirus (MCMV) in both the spleen and liver of MCMV-infected susceptible BALB/c mice. Significant inhibition of virus replication was observed for two different inoculum doses of virus (2 x 10(4) pfu per mouse [0.6 LD50] and 2 x 10(4.12) pfu per mouse [0.8 LD50]). Analysis of IFN retention, using [35S]-labeled IFN-alpha1 compared with the nonreceptor binding mutant IFN-alpha1 (R33M) administered orally to mice, revealed binding of wild-type IFN-alpha1 to several tissues. In particular, IFN was retained by tissues proximal to lymphoid regions, including the posterior nasal cavity, posterior tongue, small intestine, and rectum. These findings suggest that type I IFNs may inhibit MCMV replication by distal binding of the orally administered IFN to various tissues, which in turn augment the primary immune response to virus infection.

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Structure/function studies of murine interferon-α1 using site-directed mutagenesis followed by in vitro synthesis

Cited by 3 publications

References 28 publications

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

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

Synergistic role of type I interferons in the induction of protective cytotoxic T lymphocytes

Low-Dose Oral Type I Interferons Reduce Early Virus Replication of Murine CytomegalovirusIn Vivo

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