Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 366, Issue 5, Pages 1365-1373Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2006.11.095
Keywords
interleukin-4 receptor; WSXWS motif; signal transduction; membrane biophysics; free energy perturbation
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Funding
- NIGMS NIH HHS [GM62838] Funding Source: Medline
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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.
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