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Protein Sci. 1993 Jan;2(1):55-70.

Modeling alpha-helical transmembrane domains: the calculation and use of substitution tables for lipid-facing residues.

Author information

1
Department of Crystallography, Birkbeck College, London, United Kingdom.

Abstract

Amino acid substitution tables are calculated for residues in membrane proteins where the side chain is accessible to the lipid. The analysis is based upon the knowledge of the three-dimensional structures of two homologous bacterial photosynthetic reaction centers and alignments of their sequences with the sequences of related proteins. The patterns of residue substitutions show that the lipid-accessible residues are less conserved and have distinctly different substitution patterns from the inaccessible residues in water-soluble proteins. The observed substitutions obtained from sequence alignments of transmembrane regions (identified from, e.g., hydrophobicity analysis) can be compared with the patterns derived from the substitution tables to predict the accessibility of residues to the lipid. A Fourier transform method, similar to that used for the calculation of a hydrophobic moment, is used to detect periodicity in the predicted accessibility that is compatible with the presence of an alpha-helix. If the putative transmembrane region is identified as helical, then the buried and exposed faces can be discriminated. The presence of charged residues on the lipid-exposed face can help to identify the regions that are in contact with the polar environment on the borders of the bilayer, and the construction of a meaningful three-dimensional model is then possible. This method is tested on an alignment of bacteriorhodopsin and two related sequences for which there are structural data at near atomic resolution.

PMID:
8443590
PMCID:
PMC2142307
DOI:
10.1002/pro.5560020106
[Indexed for MEDLINE]
Free PMC Article

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