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

FEBS Letters

Kurapkat, Günther²  Aarden, Lucien A.³  Bos, Hanny Klaasse³  Grötzinger, Joachim²  Ebeling, Saskia B.³  Brakenhoff, Just.P.J.³  Rose-John, Stefan¹  de Hon, Floris D.³ 

[1] I. Medical Clinic, Section Pathophysiology, Mainz University, Mainz, Germany;Department of Biochemistry, RWTH Aachen, Aachen, Germany;Department of Autoimmune Disease, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands

关键词: Interleukin-6;    Structure-function analysis;    gp130;   

DOI  :  10.1016/0014-5793(95)00741-Q

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α-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-α-chain-dependent binding to the IL-6 signal transducer, gp130.

【 授权许可】

Unknown