How do Proteins Cross a Membrane?

Abstract

The questions. Classical studies by Palade, deDuve, and colleagues established that membranes divide cells into distinct compartments, each with a unique set of resident proteins catalyzing distinct functions. Each compartment is either a membrane, with its own set of embedded proteins, or a soluble space surrounded by a membrane. A typical eukaryotic cell may have over 20 compartments, while a bacterium such as E. coli has four the cytoplasm, inner [plasma] membrane, periplasm, and outer membrane. In contrast, almost all protein synthesis begins in the cytosol in all cells, in a basically spatially undifferentiated manner. The first question then is how proteins are targeted, either to remain in the cytosol or to the appropriate membrane for translocation. Having arrived there, the second question is one of translocation mechanism. Is it by radically changing its structure to pass from the aqueous cytosol to the hydrocarbon-like interior of a membrane, or by a proteinaceous transport system (“translocase”)? In either case, what is the energy source for this transfer? Is it the energy of protein synthesis pushing the chain out of the ribosome, a pulling force on the other side, electrophoresis, or is metabolic energy coupled to protein translocation by translocase? In Fig. 1, these questions are illustrated, with a fig leaf both conveying the attractive quality of the hidden solution and covering our ignorance about the ultimate answers.

Work in the authors’ laboratory is supported by the Insititute of General Medical Sciences, National Institutes of Health, USA