Conformational analyses of the Epidermal Growth Factor Receptor by hydrogen exchange measurements in the gas-phase and in solution

摘要

Gas-phaso HDX performed a few milliseconds after ionization allows conformational analyses of large biologically-important proteins at native conditions. The combination of nanoESI with gas-phase HDX permits analyses of native proteins using only very small amounts (10-20 pmol). The gas-phase HDX setup measures the exchange of sites in proteins not probed by solution HDX experiments (side-chain hydrogens vs. amide hydrogens). Solution and gas-phase HDX identify and map differences in conformation to different regions of the wildtype and oncogenic variants of the kinase Further, gas-phase experiments suggest that wildtype EGFR and mutants do not dimerize.