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D1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor.

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  • 1. Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
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    • Inoue M 1
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Proceedings of the National Academy of Sciences of the United States of America, 01 Sep 1995, 92(19):8579-8583
https://doi.org/10.1073/pnas.92.19.8579 PMID: 7567978 PMCID: PMC41009

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Abstract 

Human ciliary neurotrophic factor (hCNTF), which promotes the cell survival and differentiation of motor and other neurons, is a protein belonging structurally to the alpha-helical cytokine family. hCNTF was subjected to three-dimensional structure modeling and site-directed mutagenesis to analyze its structure-function relationship. The replacement of Lys-155 with any other amino acid residue resulted in abolishment of neural cell survival activity, and some of the Glu-153 mutant proteins had 5- to 10-fold higher biological activity. The D1 cap region (around the boundary between the CD loop and helix D) of hCNTF, including both Glu-153 and Lys-155, was shown to play a key role in the biological activity of hCNTF as one of the putative receptor-recognition sites. In this article, the D1 cap region of the 4-helix-bundle proteins is proposed to be important in receptor recognition and biological activity common to alpha-helical cytokine proteins reactive with gp130, a component protein of the receptors.

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Proc Natl Acad Sci U S A. 1995 Sep 12; 92(19): 8579–8583.
PMCID: PMC41009
PMID: 7567978

D1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor.

M Inoue, C Nakayama, K Kikuchi, T Kimura, Y Ishige, A Ito, M Kanaoka, and H Noguchi
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Abstract

Human ciliary neurotrophic factor (hCNTF), which promotes the cell survival and differentiation of motor and other neurons, is a protein belonging structurally to the alpha-helical cytokine family. hCNTF was subjected to three-dimensional structure modeling and site-directed mutagenesis to analyze its structure-function relationship. The replacement of Lys-155 with any other amino acid residue resulted in abolishment of neural cell survival activity, and some of the Glu-153 mutant proteins had 5- to 10-fold higher biological activity. The D1 cap region (around the boundary between the CD loop and helix D) of hCNTF, including both Glu-153 and Lys-155, was shown to play a key role in the biological activity of hCNTF as one of the putative receptor-recognition sites. In this article, the D1 cap region of the 4-helix-bundle proteins is proposed to be important in receptor recognition and biological activity common to alpha-helical cytokine proteins reactive with gp130, a component protein of the receptors.

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Selected References

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