Class 1 cytokine receptors regulate essential biological processes through complex intracellular signaling networks. However, the structural platform for understanding their functions is currently incomplete as structure-function studies of the intracellular domains (ICDs) are critically lacking. This study presents the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin and growth hormone receptor ICDs are intrinsically disordered throughout their entire lengths. We show that they interact specifically with hallmark lipids of the inner plasma membrane leaflet through conserved motifs resembling immuno T-cell receptor activation motifs(ITAMs) . However, contrary to the observations made for ITAMs, lipid association of the prolactin and growth hormone receptor ICDs was shown to be unaccompanied by changes in transient secondary structure and independent of tyrosine phosphorylation. The data presented here provides a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signaling.
- Copyright 2015 The Author(s)
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