The solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor

✍ Scribed by Hecht, Oliver; Dingley, Andrew J.; Schwanter, Andreas; Özbek, Suat; Rose-John, Stefan; Grötzinger, Joachim

• Book ID: 126076589
• Publisher: Walter de Gruyter GmbH & Co. KG
• Year: 2006
• Tongue: English
• Weight: 202 KB
• Volume: 387
• Category: Article
• ISSN: 1431-6730
• DOI: 10.1515/BC.2006.155

✦ Synopsis

Abstract

The members of the interleukin-6-type family of cytokines interact with receptors that have a modular structure and are built of several immunoglobulin-like and fibronectin type III-like domains. These receptors have a characteristic cytokine receptor homology region consisting of two fibronectin type III-like domains defined by a set of four conserved cysteines and a tryptophan-serine-X-tryptophan-serine sequence motif. On target cells, interleukin-6 (IL-6) initially binds to its cognate α-receptor and subsequently to a homodimer of the signal transducer receptor gp130. The IL-6 receptor (IL-6R) consists of three extracellular domains. The N-terminal immunoglobulin-like domain is not involved in ligand binding, whereas the third membrane-proximal fibronectin-like domain (IL-6R-D3) accounts for more than 90% of the binding energy to IL-6. Here, we present the solution structure of the IL-6R-D3 domain solved by multidimensional heteronuclear NMR spectroscopy.