title: Amino acid composition analysis of human secondary transport proteins and implications for reliable membrane topology prediction.
abstract: Secondary transporters in humans are a large group of proteins that transport a wide range of ions, metals, organic and inorganic solutes involved in energy transduction, control of membrane potential and osmotic balance, metabolic processes and in the absorption or efflux of drugs and xenobiotics. They are also emerging as important targets for development of new drugs and as target sites for drug delivery to specific organs or tissues. We have performed amino acid composition (AAC) and phylogenetic analyses and membrane topology predictions for 336 human secondary transport proteins and used the results to confirm protein classification and to look for trends and correlations with structural domains and specific substrates and/or function. Some proteins showed statistically high contents of individual amino acids or of groups of amino acids with similar physicochemical properties. One recurring trend was a correlation between high contents of charged and/or polar residues with misleading results in predictions of membrane topology, which was especially prevalent in Mitochondrial Carrier family proteins. We demonstrate how charged or polar residues located in the middle of transmembrane helices can interfere with their identification by membrane topology tools resulting in missed helices in the prediction. Comparison of AAC in the human proteins with that in 235 secondary transport proteins from Escherichia coli revealed similar overall trends along with differences in average contents for some individual amino acids and groups of similar amino acids that are presumed to result from a greater number of functions and complexity in the higher organism.
authors.affiliation: a Department of Molecular Medicine and Genetics, Research Centre for Molecular Medicine, School of Medicine , Hamadan University of Medical Sciences , Hamadan , Iran.
authors.forename: Massoud
authors.initials: M
authors.lastname: Saidijam
authors.affiliation: a Department of Molecular Medicine and Genetics, Research Centre for Molecular Medicine, School of Medicine , Hamadan University of Medical Sciences , Hamadan , Iran.
authors.forename: Sonia
authors.initials: S
authors.lastname: Azizpour
authors.affiliation: b School of BioMedical Sciences and the Astbury Centre for Structural Molecular Biology , University of Leeds , Leeds LS2 9JT , UK.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Patching
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D001426:Bacterial Proteins; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D030562:Databases, Protein; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins
keywords: amino acid composition; drug targets; human transport proteins; membrane topology; structure