Lipid-protein interactions drive membrane protein topogenesis in accordance with the positive inside rule

Mikhail Bogdanov, Jun Xie, William Dowhan

Research output: Contribution to journalShort survey

53 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9637-9641
Number of pages5
JournalJournal of Biological Chemistry
Issue number15
Publication statusPublished - Apr 10 2009


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this