The solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor.
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 alpha-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.
Hecht
Oliver
O
Biochemisches Institut der Christian-Albrechts-Universität Kiel, Olshausenstr. 40, D-24118 Kiel, Germany.
Dingley
Andrew J
AJ
Schwanter
Andreas
A
Ozbek
Suat
S
Rose-John
Stefan
S
Grötzinger
Joachim
J
D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D019947:Receptors, Interleukin-6 / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry
D000939:Epitopes; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D012996:Solutions