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J Biol Chem. 2009 Apr 10;284(15):9637-41. doi: 10.1074/jbc.R800081200. Epub 2008 Dec 12.

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

Author information

  • 1Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas 77030, USA. mikhail.v.bogdanov@uth.tmc.edu

Abstract

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.

PMID:
19074771
[PubMed - indexed for MEDLINE]
PMCID:
PMC2665083
Free PMC Article
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