Snorkeling preferences foster an amino acid composition bias in transmembrane helices.
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.
Chamberlain
Aaron K
AK
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.
Lee
Yohan
Y
Kim
Sanguk
S
Bowie
James U
JU
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation
D000596:Amino Acids; D008565:Membrane Proteins