D1 CAP REGION INVOLVED IN THE RECEPTOR RECOGNITION AND NEURAL CELL-SURVIVAL ACTIVITY OF HUMAN CILIARY NEUROTROPHIC FACTOR

被引：26

作者：

INOUE, M ^{[1
]}

NAKAYAMA, C ^{[1
]}

KIKUCHI, K ^{[1
]}

KIMURA, T ^{[1
]}

ISHIGE, Y ^{[1
]}

ITO, A ^{[1
]}

KANAOKA, M ^{[1
]}

NOGUCHI, H ^{[1
]}

机构：

[1] SUMITOMO PHARMACEUT CO LTD,KONOHANA KU,OSAKA 554,JAPAN

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1995年 / 92卷 / 19期

关键词：

MUTAGENESIS; CYTOKINE; GLYCOPROTEIN GP130; ANTAGONIST;

D O I：

10.1073/pnas.92.19.8579

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：8579 / 8583

页数：5

共 35 条

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