The positive inside rule is not determined by the polarity of the delta psi (transmembrane electrical potential)

• Published in: Molecular microbiology Vol. 29; no. 4; pp. 1125 - 1126
• Main Authors: van de Vossenberg, J L, Albers, S V, van der Does, C, Driessen, A J, van Klompenburg, W
• Format: Journal Article
• Language: English
• Published: England 01.08.1998
• Subjects: Animals; Archaea - metabolism; Bacteria - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Electron Transport Complex IV - chemistry; Electron Transport Complex IV - metabolism; Escherichia coli Proteins; Eukaryotic Cells; Membrane Potentials; Membrane Proteins - chemistry; Membrane Proteins - metabolism; SEC Translocation Channels; Sulfolobus acidocaldarius
• ISSN: 0950-382X
• DOI: 10.1046/j.1365-2958.1998.01001.x

The transmembrane orientation of integral membrane proteins from many sources is described by the so-called cis-positive or positive-inside rule. The positively charged amino acid residues arginine and lysine are enriched in cytoplasmic domains and extremely rare in extracytoplasmic domains. It has been suggested that the transmembrane electrical potential, Delta psi , is the main determinant of the topology of membrane proteins. In most organisms, the Delta psi is inside negative and outside positive and is supposed to retard the transmembrane pasage of positive charges. Here, we report data that contradict such an essential role for Delta psi in determining the asymmetric distribution of positive charges of membrane proteins. Obligate acidophiles, such as Sulfolobus acidocaldarius, are organisms that thrive at very low environmental pH values (pH 0.5-2.5). These organisms maintain their intracellular pH near neutrality. As a result of the massive transmembrane pH gradient, acidophiles have a reversed Delta psi , i.e. inside positive instead of negative. If the Delta psi were a major cause of the positive inside rule, an inversed charge distribution is expected for membrane proteins of acidophiles. To test this prediction, we searched databanks for proteins with known topology that also exist in acidophiles. We focused on the homologues of SecY, a subunit of the precursor protein translocase, and on subunit 1 of cytochrome c oxidase.