Control of membrane protein topology by a single C-terminal residue.
The mechanism by which multispanning helix-bundle membrane proteins are inserted into their target membrane remains unclear. In both prokaryotic and eukaryotic cells, membrane proteins are inserted cotranslationally into the lipid bilayer. Positively charged residues flanking the transmembrane helices are important topological determinants, but it is not known whether they act strictly locally, affecting only the nearest transmembrane helices, or can act globally, affecting the topology of the entire protein. Here we found that the topology of an Escherichia coli inner membrane protein 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 C terminus. This observation points to an unanticipated plasticity in membrane protein insertion mechanisms.
Seppälä
Susanna
S
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Slusky
Joanna S
JS
Lloris-Garcerá
Pilar
P
Rapp
Mikaela
M
von Heijne
Gunnar
G
D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000737:chemistry* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004996:Ethidium / Q000494:pharmacology; D008051:Lipid Bilayers; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D015202:Protein Engineering; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D017920:Antiporters; D029968:Escherichia coli Proteins; D008051:Lipid Bilayers; D026901:Membrane Transport Proteins; D050505:Mutant Proteins; C075436:EmrE protein, E coli; D004996:Ethidium