Inoue M, Nakayama C, Kikuchi K, Kimura T, Ishige Y, Ito A, Kanaoka M, Noguchi H
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8579-83. doi: 10.1073/pnas.92.19.8579.
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.
人睫状神经营养因子（hCNTF）可促进运动神经元和其他神经元的细胞存活与分化，它在结构上属于α-螺旋细胞因子家族的一种蛋白质。对hCNTF进行了三维结构建模和定点诱变，以分析其结构-功能关系。用任何其他氨基酸残基取代Lys-155都会导致神经细胞存活活性丧失，并且一些Glu-153突变蛋白具有高5至10倍的生物活性。hCNTF的D1帽区域（围绕CD环与螺旋D之间的边界），包括Glu-153和Lys-155，作为假定的受体识别位点之一，在hCNTF的生物活性中起关键作用。在本文中，提出4-螺旋束蛋白的D1帽区域对于与受体的组成蛋白gp130反应的α-螺旋细胞因子蛋白共有的受体识别和生物活性很重要。
