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

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.

SUBMITTER: Bogdanov M

PROVIDER: S-EPMC2665083 | biostudies-other | 2009 Apr

REPOSITORIES: biostudies-other

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

Bogdanov Mikhail M Xie Jun J Dowhan William W

The Journal of biological chemistry 20081212 15

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 prote ...[more]

PMID: 19074771

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