Conservation of Functional Sites on Interleukin-6 and Implications for Evolution of Signaling Complex Assembly and Therapeutic Intervention

0384494 - ÚOCHB 2013 RIV US eng J - Journal Article
Veverka, Václav - Baker, T. - Redpath, N. T. - Carrington, B. - Muskett, F. W. - Taylor, R. J. - Lawson, A. D. G. - Henry, A. J. - Carr, M. D.
Conservation of Functional Sites on Interleukin-6 and Implications for Evolution of Signaling Complex Assembly and Therapeutic Intervention.
Journal of Biological Chemistry. Roč. 287, č. 47 (2012), s. 40043-40050. ISSN 0021-9258. E-ISSN 1083-351X
Institutional research plan: CEZ:AV0Z40550506
Keywords : interleukin-6 * cell signalling * NMR
Subject RIV: CE - Biochemistry
Impact factor: 4.651, year: 2012

A number of secreted cytokines, such as interleukin-6 (IL-6), are attractive targets for the treatment of inflammatory diseases. We have determined the solution structure of mouse IL-6 to assess the functional significance of apparent differences in the receptor interaction sites (IL-6Ralpha and gp130) suggested by the fairly low degree of sequence similarity with human IL-6. Structure-based sequence alignment of mouse IL-6 and human IL-6 revealed surprising differences in the conservation of the two distinct gp130 binding sites (IIa and IIIa), which suggests a primacy for site III-mediated interactions in driving initial assembly of the IL-6/IL-6Ralpha/gp130 ternary complex.
Permanent Link: http://hdl.handle.net/11104/0214121