title: Membrane composition influences the topology bias of bacterial integral membrane proteins.
abstract: Small multidrug resistance (SMR) protein family members confer bacterial resistance to toxic antiseptics and are believed to function as dual topology oligomers. If dual topology is essential for SMR activity, then the topology bias should change as bacterial membrane lipid compositions alter to maintain a "neutral" topology bias. To test this hypothesis, a bioinformatic analysis of bacterial SMR protein sequences was performed to determine a membrane protein topology based on charged amino acid residues within loops, and termini regions according to the positive inside rule. Three bacterial lipid membrane parameters were examined, providing the proportion of polar lipid head group charges at the membrane surface (PLH), the relative hydrophobic fatty acid length (FAL), and the proportion of fatty acid unsaturation (FAU). Our analysis indicates that individual SMR pairs, and to a lesser extent SMR singleton topology biases, are significantly correlated to increasing PLH, FAL and FAU differences validating the hypothesis. Correlations between the topology biases of SMR proteins identified in Gram+ compared to Gram- species and each lipid parameter demonstrated a linear inverse relationship.
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Denice C
authors.initials: DC
authors.lastname: Bay
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Turner
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry* / Q000378:metabolism; D000890:Anti-Infective Agents / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism*; D015233:Models, Statistical; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013045:Species Specificity
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D005227:Fatty Acids; D008055:Lipids; D008565:Membrane Proteins