title: Snorkeling preferences foster an amino acid composition bias in transmembrane helices.
abstract: By analyzing transmembrane (TM) helices in known structures, we find that some polar amino acids are more frequent at the N terminus than at the C terminus. We propose the asymmetry occurs because most polar amino acids are better able to snorkel their polar atoms away from the membrane core at the N terminus than at the C terminus. Two findings lead us to this proposition: (1) side-chain conformations are influenced strongly by the N or C-terminal position of the amino acid in the bilayer, and (2) the favored snorkeling direction of an amino acid correlates well with its N to C-terminal composition bias. Our results suggest that TM helix predictions should incorporate an N to C-terminal composition bias, that rotamer preferences of TM side-chains are position-dependent, and that the ability to snorkel influences the evolutionary selection of amino acids for the helix N and C termini.
authors.affiliation: Department of Chemistry and Biochemistry, UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute, Boyer Hall, 611 Charles E. Young Drive E, Los Angeles, CA 90095-1570, USA.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Chamberlain
authors.forename: Yohan
authors.initials: Y
authors.lastname: Lee
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D000596:Amino Acids; D008565:Membrane Proteins