Beyond dimerization: A membrane-dependent activation model for interleukin-4 receptor-mediated signalling

Thomas Weidemann, Siegfried Hoefinger, Kurt Mueller, Manfred Auer

Research output: Contribution to journalArticlepeer-review

Abstract

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. (c) 2006 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1365-1373
Number of pages9
JournalJournal of Molecular Biology
Volume366
Issue number5
DOIs
Publication statusPublished - 9 Mar 2007

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