The signal transducer gp130: Solution structure of the carboxy‐terminal domain of the cytokine receptor homology region

Kernebeck, Thomas; Pflanz, Stefan; Müller‐Newen, Gerhard; Kurapkat, Günther; Scheek, Ruud M.; Dijkstra, Klaas; Heinrich, Peter C.; Wollmer, Axel; Grzesiek, Stephan; Grötzinger, Joachim

doi:10.1110/ps.8.1.5

Cited by 25 publications

(2 citation statements)

References 47 publications

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“…There are presently five other solution structures of unbound cytokine receptors with a WS motif available; the human interleukin-6 receptor (IL6R) (Hecht et al, 2006), the cytokinebinding-domain of the common b chain of the receptor for granulocyte macrophage colony-stimulating factor (D4b c ) (Mulhern et al, 2000), the granulocyte colony stimulating factor receptor (Yamasaki et al, 1997), the signal transducer gp130 (Kernebeck et al, 1999), and the C-terminal domain of the ciliary neurotrophic factor receptor (CNTFR) (Man et al, 2003). In all but D4b c and CNTFR, there are missing assignments for Trp/Arg ladder residues.…”

Section: Structurementioning

confidence: 99%

The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor

et al. 2012

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The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state. By contrast, in the hormone bound state, a Trp/Arg-ladder is formed. The conformational change is hormone-dependent and influences the receptor-receptor dimerization site 3. In the constitutively active, breast cancer-related receptor mutant PRLR(I146L), we observed a stabilization of the dimeric state and a change in the dynamics of the motif. Here we demonstrate a structural link between the WSXWS motif, hormone binding, and receptor dimerization and propose it as a general mechanism for class 1 receptor activation.

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Section: Structurementioning

confidence: 99%

The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor

et al. 2012

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“…A variety of amino acids can occur at the position "X". WSEWS sequence can be found in the IL-6Rα chain (Biró et al, 1995); WSDWS motif is present in gp130 molecule (Hilton et al, 1996, Kernebeck et al, 1999, while erythropoetin receptor contains a WSAWS motif (Furmanek et al, 2003). Meissner and coworkers found that WSKWS sequence was essential for the inhibition of cytokine signaling mediated by common γ chain of the soluble cytokine receptor in mice (Meissner et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Effect of SXWS/WSXWS peptides on chemotaxis and adhesion of the macrophage‐like cell line J774

Szabó

Láng

Lang

et al. 2015

J of Molecular Recognition

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WSXWS motif is a conserved amino acid sequence which is present in type I cytokine receptors. This motif that can be found both in the ligand binding chains and signal transducer molecule of the receptors with different amino acids at the position 'X', plays a role in the receptor folding, ligand binding and signal transduction as well. Structural analysis proved that WSEWS motif of IL-6R is located in a highly accessible location in the protein.Structural properties and chemotaxis of a tetrapeptide library with SXWS sequence, where X was the 19 proteinogenic amino acids except cystein were systematically studied earlier. It has been proved that C-terminal amidation and the identity of amino acid 'X' had a pronounced influence on the chemotactic properties, but less of the structure of the peptides. Here we present our findings on the effect of a tetra-and a pentapeptide library with the sequence of SXWS and WSXWS on the chemotaxis and adhesion of J774 murine macrophage cell line. We studied the effect of the presence/absence of N-terminal tryptophan and the different amino acids at the 'X' position on these physiological responses. Results indicated that amino acid 'X' had a marked influence on chemotaxis, adhesion as well as on proliferation induced by (W)SXWS peptides. Elongation of SXWS sequence with a tryptophan at the N terminus also altered pronouncedly all the physiological responses of the cells studied. A good correlation could be observed between the chemotaxis and the proliferation and physicochemical parameters of the amino acid 'X'.2

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CEREBROSPINAL FLUID AND SERUM PROTEIN LEVELS OF TUMOUR NECROSIS FACTOR-ALPHA (TNF-α), INTERLEUKIN-6 (IL-6) AND SOLUBLE INTERLEUKIN-6 RECEPTOR (sIL-6R gp80) IN MULTIPLE SCLEROSIS PATIENTS

et al. 2002

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The signal transducer gp130: Solution structure of the carboxy‐terminal domain of the cytokine receptor homology region

Cited by 25 publications

References 47 publications

The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor

The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor

Effect of SXWS/WSXWS peptides on chemotaxis and adhesion of the macrophage‐like cell line J774

CEREBROSPINAL FLUID AND SERUM PROTEIN LEVELS OF TUMOUR NECROSIS FACTOR-ALPHA (TNF-α), INTERLEUKIN-6 (IL-6) AND SOLUBLE INTERLEUKIN-6 RECEPTOR (sIL-6R gp80) IN MULTIPLE SCLEROSIS PATIENTS

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