Spectroscopy and modelling of the cytoplasmic domain of the gamma-subunit of the high affinity immunoglobulin E receptor.

Abstract

The high affinity receptor for IgE, Fc epsilon RI, is responsible for immediate hypersensitivity reactions. In rodents Fc epsilon RI is a tetrameric complex, alpha beta gamma 2 of non-covalently attached subunits: one IgE-binding alpha subunit with the binding site in the extracellular part of the chain, one beta-subunit and a dimer of disulphide linked gamma-subunits. Although there is an increasing evidence that the gamma-subunit chains are important signalling proteins that appear to function through a common Tyr-Leu-Tyr-Leu amino acid motif present in their cytoplasmic tails, which link the ligand binding specificity of their associated chains to signal transduction pathways, many questions related to conformation and function of this subunit remain to be answered. In the present work, the 36-residue cytoplasmic domain of the gamma-subunit has been synthesized and conformational studies by the combined use of Fourier transform infrared (FTIR), circular dichroism (CD) and nuclear magnetic resonance (NMR) have been performed. Based on the constraints found by these methods, conformational models of the cytoplasmic tail of the gamma-subunit are proposed and discussed.