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Advances in structure determination of membrane proteins enable analysis of the propensities of amino acids in extramembrane versus transmembrane locations to be performed on the basis of structure rather than of sequence and predicted topology. Using 29 available structures of integral membrane proteins with resolutions better than 4 A the distributions of amino acids in the transmembrane domains were calculated. The results were compared to analysis based on just the sequences of the same transmembrane alpha-helices and significant differences were found. The distribution of residues between transmembrane alpha-helices and beta-strands was also compared. Large hydrophobic (Phe, Leu, Ile, Val) residues showed a clear preference for the protein surfaces facing the lipids for beta-barrels, but in alpha-helical proteins no such preference was seen, with these residues equally distributed between the interior and the surface of the protein. A notable exception to this was alanine, which showed a slight preference for the interior of alpha-helical membrane proteins. Aromatic residues were found to follow saddle-like distributions preferring to be located in the lipid/water interfaces. The resultant 'aromatic belts' were spaced more closely for beta-barrel than for alpha-helical membrane proteins. Charged residues could be shown to generally avoid surfaces facing the bilayer although they were found to occur frequently in the transmembrane region of beta-barrels. Indeed detailed comparison between alpha-helical and beta-barrel proteins showed many qualitative differences in residue distributions. This suggests that there may be subtle differences in the factors stabilising beta-barrels in bacterial outer membranes and alpha-helix bundles in all other membranes.

Type

Journal article

Journal

Biochim Biophys Acta

Publication Date

02/05/2001

Volume

1512

Pages

1 - 14

Keywords

Amino Acids, Animals, Bacteria, Glycine, Humans, Lipid Bilayers, Membrane Proteins, Methods, Proline, Protein Structure, Secondary, Statistics as Topic