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1: J Mol Biol. 2007 Mar 9;366(5):1365-73. Epub 2006 Dec 6.
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Beyond dimerization: a membrane-dependent activation model for interleukin-4 receptor-mediated signalling.

Weidemann T, Höfinger S, Müller K, Auer M.

Innovative Screening Technologies, Novartis Institutes for BioMedical Research, Brunnerstr 59, A-1235 Vienna, Austria. tj.weidemann@web.de

Class I cytokine receptors efficiently transfer activation signals from the extracellular space to the cytoplasm and play a dominant role in growth control and differentiation of human tissues. Although a significant body of literature is devoted to this topic, a consistent mechanistic picture for receptor activation in the membrane environment is still missing. Using the interleukin-4 receptor (IL-4R) as an example, we propose that the membrane-proximal stem-loop of the extracellular domains contains pivotal elements of a rotational switch. Interfacial energies of amino acid side-chains contained in the highly conserved WSXWS at the surface of the lipid bilayer suggest a new functional role for this motif. A generic activation mechanism for this receptor class is presented, which may impact the design of a new generation of biophysical assay systems.

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PMID: 17223132 [PubMed - indexed for MEDLINE]