Exploring the inner membrane proteome of Escherichia coli: which proteins are eluding detection and why?

Proteins embedded in membranes are important for helping the cell adapt to changes in the extracellular milieu and often play key roles in the life cycles of pathogenic microbes. Bioinformatic predictions can provide an estimate of membrane proteins, but experimental approaches of detection are required for a deeper understanding of their functions. To determine the effectiveness of experimental detection approaches, here we collate and discuss data from available proteomic analyses on the inner (or cytoplasmic) membrane of Escherichia coli. We compile a list of proteins that have been experimentally detected and by comparing this to a predicted proteome we identify membrane proteins that have eluded us experimentally. Limitations of current proteomic analyses together with possible solutions are discussed. We also provide a list of proteins for benchmarking the performance of future proteomic studies.