LEUCINE-58 IN THE PUTATIVE 5TH HELICAL REGION OF HUMAN INTERLEUKIN (IL)-6 IS IMPORTANT FOR ACTIVATION OF THE IL-6 SIGNAL TRANSDUCER, GP130

被引:9
|
作者
DEHEN, FD
BOS, HK
EBELING, SB
GROTZINGER, J
KURAPKAT, G
ROSEJOHN, S
AARDEN, LA
BRAKENHOFF, JPJ
机构
[1] NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,DEPT AUTOIMMUNE DIS,1066 CX AMSTERDAM,NETHERLANDS
[2] UNIV AMSTERDAM,CLIN & EXPTL IMMUNOL LAB,1066 CX AMSTERDAM,NETHERLANDS
[3] RHEIN WESTFAL TH AACHEN,DEPT BIOCHEM,W-5100 AACHEN,GERMANY
[4] UNIV MAINZ,PATHOPHYSIOL SECT,MED CLIN 1,W-6500 MAINZ,GERMANY
关键词
INTERLEUKIN-6; STRUCTURE-FUNCTION ANALYSIS; GP130;
D O I
10.1016/0014-5793(95)00741-Q
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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 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.
引用
收藏
页码:187 / 191
页数:5
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