Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Human interleukin-11 (hIL-11) is a pleiotropic cytokine administered to patients for recovering low platelet counts. From a structural point of view hIL-11 belongs to the long-helix cytokine superfamily, which is characterized by a conserved core motif consisting of four alpha-helices. We have investigated the region of hIL-11 that does not belong to the alpha-helical bundle motif, which we have termed “non-core region”. The interleukin was N- or O-glycosylated at specific positions within the non-core region, and the functional consequences of these modifications were examined in cell-based as well as biophysical assays. The data indicated that the non-core region modulates the function of hIL-11 in two ways. First, most of the muteins displayed enhanced cell-stimulatory properties (super-agonist behavior) in a glycosylation-dependent manner, suggesting that the non-core region is biologically designed to limit the cell-proliferative potential of hIL-11. Second, glycosylation of a predicted mini alpha-helix led to cytokine inactivation, demonstrating that this structural element interacts with a second gp130 receptor. These findings have unveiled new and unexpected elements modulating the biological activity of hIL-11, which may be exploited to develop more versatile medications based on this important cytokine. Yanaka S et al. J. Biol. Chem. in press. (2011)</jats:p>