Dependence of α-helical and β-sheet amino acid propensities on the overall protein fold type

Abstract

Background: A large number of studies have been carried out to obtain amino acid propensities for α-helices and β-sheets. The obtained propensities for α-helices are consistent with each other, and the pair-wise correlation coefficient is frequently high. On the other hand, the β-sheet propensities obtained by several studies differed significantly, indicating that the context significantly affects β-sheet propensity.

Results: We calculated amino acid propensities for α-helices and β-sheets for 39 and 24 protein folds, respectively, and addressed whether they correlate with the fold. The propensities were also calculated for exposed and buried sites, respectively. Results showed that α-helix propensities do not differ significantly by fold, but β-sheet propensities are diverse and depend on the fold. The propensities calculated for exposed sites and buried sites are similar for α-helix, but such is not the case for the β-sheet propensities. We also found some fold dependence on amino acid frequency in β-strands. Folds with a high Ser, Thr and Asn content at exposed sites in β-strands tend to have a low Leu, Ile, Glu, Lys and Arg content (correlation coefficient = -0.90) and to have flat β-sheets. At buried sites in β-strands, the content of Tyr, Trp, Gln and Ser correlates negatively with the content of Val, Ile and Leu (correlation coefficient = -0.93). "All-β" proteins tend to have a higher content of Tyr, Trp, Gln and Ser, whereas "α/β" proteins tend to have a higher content of Val, Ile and Leu.

Conclusions: The α-helix propensities are similar for all folds and for exposed and buried residues. However, β-sheet propensities calculated for exposed residues differ from those for buried residues, indicating that the exposed-residue fraction is one of the major factors governing amino acid composition in β-strands. Furthermore, the correlations we detected suggest that amino acid composition is related to folding properties such as the twist of a β-strand or association between two β sheets.

Figure 1

Amino acid propensities for each SCOP fold. Box plots of amino acid propensities for each SCOP fold for α-helices (A) and β-strands (B). Each box encloses 50% of the data with the median value displayed as a line. The top and bottom of the box mark the limits of ±25% of the data. The lines extending from the top and bottom of each box mark the minimum and maximum values within the data set that fall within an acceptable range. Any value outside of this range, called an outlier, is displayed as an individual point. Underlining of certain residues (one-letter code) on the horizontal axis denotes that the results from the Fisher-Irwin population proportion test indicated that differences in propensities are statistically significant between folds.

Figure 2

Amino acid propensities for exposed and buried residues. Box plots of Amino acid propensities for each SCOP fold for exposed (A) and buried (B) residues in α-helices and for exposed (C) and buried (D) residues in β-strands. The propensities for β-strands for Trp in the “PH domain-like barrel” SCOP fold and for Lys in the “Protein kinase-like” SCOP fold were out of range (4.3 in C and 3.8 in D, respectively) and are not shown. Underlining of certain residues on the horizontal axis denotes that the results from the Fisher-Irwin population proportion test indicated that differences in propensities are statistically significant between folds.

Figure 3

Correlation coefficients between amino acid propensities. Correlation coefficients between amino acid propensities for α-helices (A) and β-strands (B). Strong negative correlations (R < −0.7) are indicated by dark blue, and positive correlations (R > 0.7) are indicated by dark red. Comparatively strong negative correlations (R < −0.5) are indicated by light blue and positive correlations (R > 0.5) by pink.

Figure 4

Relationship between the amino acid propensities. Amino acid propensities, P, for Glu and Lys for each SCOP fold for α-helices (A) and β-strands (B). The SCOP classes are: all-α proteins (○), α/β proteins (□), α + β proteins (Δ) and all-β proteins (+).

Figure 5

Correlation coefficients between α-helix propensities for exposed residues and buried residues. Correlation coefficients between α-helix propensities for exposed residues (A) and buried residues (B). Strong negative correlations (R < −0.7) are indicated by dark blue, and positive correlations (R > 0.7) are indicated by dark red. Comparatively strong negative correlations (R < −0.5) are indicated by light blue and positive correlations (R > 0.5) by pink.

Figure 6

Correlation coefficients between β-sheet propensities for exposed residues and buried residues. Correlation coefficients between β-sheet propensities for exposed residues (A) and buried residues (B). Strong negative correlations (R < −0.7) are indicated by dark blue, and positive correlations (R > 0.7) are indicated by dark red. Comparatively strong negative correlations (R < −0.5) are indicated by light blue and positive correlations (R > 0.5) by pink.

Figure 7

Relationship between the frequencies of buried residues. Relationship between the frequencies of buried Val, Ile and Leu residues, f _VIL , and buried Trp, Tyr, Gln and Ser residues, f _WYQS , in β-strands. The SCOP classes are: α/β proteins (□), α + β proteins (Δ) and all-β proteins (+).

Figure 8

Relationship between the frequencies of exposed residues. Relationship between the frequencies of exposed Ile, Leu, Glu, Lys and Arg residues, f _ILEKR , and exposed Ser, Thr and Asn residues, f _STN , in β-strands. The SCOP classes are: α/β proteins (□), α + β proteins (Δ) and all-β proteins (+).

Figure 9

Amino acid residues on β-strands of three folds. Amino acid residues in β-strands of concanavalin A (A, B and C, PDB ID:1IOA), DS β-helix (D and E, PDB ID:1ODM), and TIM barrel (F and G, PDB ID:1SFS). The residues for α-helices are colored magenta, and those for β-strands are colored yellow. The side chains of residues in β-strands are colored by atom type (nitrogen: blue, oxygen: red, carbon: grey) in C.