Lipid-protein interactions drive membrane protein topogenesis in accordance with the positive inside rule.
Transmembrane domain orientation within some membrane proteins is dependent on membrane lipid composition. Initial orientation occurs within the translocon, but final orientation is determined after membrane insertion by interactions within the protein and between lipid headgroups and protein extramembrane domains. Positively and negatively charged amino acids in extramembrane domains represent cytoplasmic retention and membrane translocation forces, respectively, which are determinants of protein orientation. Lipids with no net charge dampen the translocation potential of negative residues working in opposition to cytoplasmic retention of positive residues, thus allowing the functional presence of negative residues in cytoplasmic domains without affecting protein topology.
Bogdanov
Mikhail
M
Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas 77030, USA. mikhail.v.bogdanov@uth.tmc.edu
Xie
Jun
J
Dowhan
William
W
D000596:Amino Acids / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry; D008954:Models, Biological; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods; D021381:Protein Transport
D000596:Amino Acids; D029968:Escherichia coli Proteins; D008051:Lipid Bilayers; D008055:Lipids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C021499:lactose permease