Control of Membrane Protein Topology by a Single C-Terminal Residue

In, Out, Positive Charge About The mechanism by which multispanning, helix-bundle membrane proteins are inserted into their target membrane is not completely understood. EmrE is an Escherichia coli inner-membrane protein with four transmembrane helices that can take up two distinct topologies—with its amino terminus toward the cytosol, or away from the cytosol. Seppälä et al. (p. 1698 , published online 27 May; see the Perspective by Tate ) exploited the dual-topology property of EmrE to study the mechanism of membrane protein assembly in Escherichia coli . Systematically exploring the effects of positively charged residues on the topology of EmrE revealed that the membrane orientation of EmrE constructs with four or five transmembrane helices could be controlled by a single positively charged residue placed in different locations throughout the protein, including the very carboxyl terminus. Such global control of membrane protein topology raises important questions concerning how multispanning membrane proteins are handled by the membrane protein insertion machinery.