人白细胞介素（IL）-6假定的第5个螺旋区域中的亮氨酸-58对于IL-6信号转导子gp130的激活很重要。

Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130.

作者信息

de Hon F D, Klaasse Bos H K, Ebeling S B, Grötzinger J, Kurapkat G, Rose-John S, Aarden L A, Brakenhoff J P

机构信息

Department of Autoimmune Diseases, University of Amsterdam, The Netherlands.

出版信息

FEBS Lett. 1995 Aug 7;369(2-3):187-91. doi: 10.1016/0014-5793(95)00741-q.

DOI:10.1016/0014-5793(95)00741-q

PMID:7649255

Abstract

A model of the tertiary structure of human IL-6, derived from the crystal-structure of granulocyte-colony stimulating factor, reveals a 5th helical region in the loop between the first and second alpha-helix. To investigate the importance of this region for biological activity of IL-6, residues Glu-52, Ser-53, Ser-54, Lys-55, Glu-56, Leu-58, and Glu-60 were individually replaced by alanine. IL-6.Leu-58Ala displayed a 5-fold reduced biological activity on the IL-6 responsive human cell lines XG-1 and A375. This reduction in bioactivity was shown to be due to a decreased capacity of the mutant protein to trigger IL-6 receptor-alpha-chain-dependent binding to the IL-6 signal transducer, gp130.

摘要

源自粒细胞集落刺激因子晶体结构的人白细胞介素-6三级结构模型显示，在第一和第二α-螺旋之间的环中有一个第五螺旋区域。为了研究该区域对白细胞介素-6生物活性的重要性，将谷氨酸-52、丝氨酸-53、丝氨酸-54、赖氨酸-55、谷氨酸-56、亮氨酸-58和谷氨酸-60的残基分别替换为丙氨酸。白细胞介素-6.亮氨酸-58丙氨酸对白细胞介素-6反应性人细胞系XG-1和A375的生物活性降低了5倍。这种生物活性的降低被证明是由于突变蛋白触发白细胞介素-6受体α链依赖性与白细胞介素-6信号转导子gp130结合的能力下降所致。