This chapter discusses the ways in which the amino acid sequence of a membrane protein dictates its insertion into the membrane and the ways in which it determines the final three dimensional fold. The chapter also focuses on membrane protein assembly that is found in the inner membrane of the bacterium Escherichia coli (E. coli) and has led to the formulation of the “positive inside” rule. The challenge that must be addressed to understand the entire assembly process is whether the formation of the topology corresponds to a distinct step in the assembly pathway, or whether the formation of the topology and the formation of the entire 3D structure are inseparable processes. Periplasmic and outer membrane E. coli proteins normally make use of the so-called Sec machinery for translocation across the inner membrane.
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