Weidemann, Thomas, Hoefinger, Siegfried, Mueller, Kurt and Auer, Manfred (2007) Beyond dimerization: a membrane-dependent activation model for interleukin-4 receptor-mediated signalling. Journal of Molecular Biology, 366 (5). pp. 1365-1373. ISSN 0022-2836

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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.jmb.2006.11.095
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	interleukin-4 receptor; WSXWS motif; signal transduction; membrane biophysics; free energy perturbation
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.jmb.2006.11.095
Date Deposited:	14 Dec 2009 13:58
Last Modified:	31 Jan 2013 01:14
URI:	https://oak.novartis.com/id/eprint/544