Abstract
BackgroundIn water-soluble proteins it is energetically favorable to bury hydrophobic residues and to expose polar and charged residues. In contrast to water soluble proteins, transmembrane proteins face three distinct environments; a hydrophobic lipid environment inside the membrane, a hydrophilic water environment outside the membrane and an interface region rich in phospholipid head-groups. Therefore, it is energetically favorable for transmembrane proteins to expose different types of residues in the different regions.ResultsInvestigations of a set of structurally determined transmembrane proteins showed that the composition of solvent exposed residues differs significantly inside and outside the membrane. In contrast, residues buried within the interior of a protein show a much smaller difference. However, in all regions exposed residues are less conserved than buried residues. Further, we found that current state-of-the-art predictors for surface area are optimized for one of the regions and perform badly in the other regions. To circumvent this limitation we developed a new predictor, MPRAP, that performs well in all regions. In addition, MPRAP performs better on complete membrane proteins than a combination of specialized predictors and acceptably on water-soluble proteins. A web-server of MPRAP is available at http://mprap.cbr.su.se/ConclusionBy including complete a-helical transmembrane proteins in the training MPRAP is able to predict surface accessibility accurately both inside and outside the membrane. This predictor can aid in the prediction of 3D-structure, and in the identification of erroneous protein structures.
Highlights
In water-soluble proteins it is energetically favorable to bury hydrophobic residues and to expose polar and charged residues
Outside the membrane solvent exposed sites consist of 19% hydrophobic residues (A, F, I, L, M and V), while buried sites consist to 49% of such residues, see Figure 1
One prominent feature of membrane proteins is that their surfaces face three distinct environments; a hydrophobic lipid environment inside the membrane, an interface environment and a hydrophilic water environment outside the membrane
Summary
In water-soluble proteins it is energetically favorable to bury hydrophobic residues and to expose polar and charged residues. In contrast to water soluble proteins, transmembrane proteins face three distinct environments; a hydrophobic lipid environment inside the membrane, a hydrophilic water environment outside the membrane and an interface region rich in phospholipid head-groups It is energetically favorable for transmembrane proteins to expose different types of residues in the different regions. A topology prediction might be a useful first step towards structure prediction, while a predictor of solvent accessibility provides complementary information Such a predictor might be useful for predicting functional relevance of individual residues, since residues responsible for e.g. catalysis or substrate binding, are often buried in the protein interior [11], while residues involved in protein-protein-interactions occur on solvent exposed sites. For water-soluble proteins many methods for predicting the accessibility have been developed [12]
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