To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology

Mikhail Bogdanov; Jun Xie; Phil Heacock; William Dowhan

doi:10.1083/jcb.200803097

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To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology

Journal article

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To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology

Mikhail Bogdanov, Jun Xie, Phil Heacock and William Dowhan

The Journal of cell biology, Vol.182(5), pp.925-935

09/08/2008

DOI: 10.1083/jcb.200803097

PMCID: PMC2528571

PMID: 18779371

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Abstract

The molecular details of how lipids influence final topological organization of membrane proteins are not well understood. Here, we present evidence that final topology is influenced by lipid–protein interactions most likely outside of the translocon. The N-terminal half of Escherichia coli lactose permease (LacY) is inverted with respect to the C-terminal half and the membrane bilayer when assembled in mutants lacking phosphatidylethanolamine and containing only negatively charged phospholipids. We demonstrate that inversion is dependent on interactions between the net charge of the cytoplasmic surface of the N-terminal bundle and the negative charge density of the membrane bilayer surface. A transmembrane domain, acting as a molecular hinge between the two halves of the protein, must also exit from the membrane for inversion to occur. Phosphatidylethanolamine dampens the translocation potential of negative residues in favor of the cytoplasmic retention potential of positive residues, thus explaining the dominance of positive over negative amino acids as co- or post-translational topological determinants.

Details

Title: Subtitle: To flip or not to flip: lipid–protein charge interactions are a determinant of final membrane protein topology
Creators: Mikhail Bogdanov - The University of Texas Health Science Center at Houston
Jun Xie - The University of Texas Health Science Center at Houston
Phil Heacock - The University of Texas Health Science Center at Houston
William Dowhan - The University of Texas Health Science Center at Houston
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.182(5), pp.925-935
DOI: 10.1083/jcb.200803097
PMID: 18779371
PMCID: PMC2528571
NLM abbreviation: J Cell Biol
ISSN: 0021-9525
eISSN: 1540-8140
Language: English
Date published: 09/08/2008
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984359692902771

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