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Limited capabilities of analytical methods to study membrane proteins The main reason behind the lack of knowledge about the early stage of signal transduction is rooted in the limitations of the used analytical methods (Yamashita et al., 2015). A key challenge to understanding the function of membrane proteins is that it is notoriously difficult to study them. The information about the stoichiometry of protein complexes is generally not obtained from intact cells but via biochemical methods involving extraction of proteins from cellular material, via X-ray crystallography of protein crystals or other technologies (Larance & Lamond, 2015; Bessman et al., 2014). Firstly, protein material is pooled from many thousands of cells and thus most knowledge about cellular function is based on population averages. Secondly, extracting the membrane proteins from the plasma membrane may lead to artefacts in conclusions about function, since the Introduction

Membrane protein stoichiometry studied in intact mammalian cells