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Comparing models of evolution for ordered and disordered proteins.

Brown CJ, Johnson AK, Daughdrill GW - Mol. Biol. Evol. (2009)

Bottom Line: Disordered proteins do not typically maintain long-range interactions, so the constraints on their evolution should be different than ordered proteins.Glutamic acid and asparagine were interesting exceptions to this result.Finally, the amino acid frequencies for disordered proteins, computed during the development of the matrices, were compared with amino acid frequencies for different categories of secondary structure in ordered proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Idaho, USA. celesteb@uidaho.edu

ABSTRACT
Most models of protein evolution are based upon proteins that form relatively rigid 3D structures. A significant fraction of proteins, the so-called disordered proteins, do not form rigid 3D structures and sample a broad conformational ensemble. Disordered proteins do not typically maintain long-range interactions, so the constraints on their evolution should be different than ordered proteins. To test this hypothesis, we developed and compared models of evolution for disordered and ordered proteins. Substitution matrices were constructed using the sequences of putative homologs for sets of experimentally characterized disordered and ordered proteins. Separate matrices, at three levels of sequence similarity (>85%, 85-60%, and 60-40%), were inferred for each type of protein structure. The substitution matrices for disordered and ordered proteins differed significantly at each level of sequence similarity. The disordered matrices reflected a greater likelihood of evolutionary changes, relative to the ordered matrices, and these changes involved nonconservative substitutions. Glutamic acid and asparagine were interesting exceptions to this result. Important differences between the substitutions that are accepted in disordered proteins relative to ordered proteins were also identified. In general, disordered proteins have fewer evolutionary constraints than ordered proteins. However, some residues like tryptophan and tyrosine are highly conserved in disordered proteins. This is due to their important role in forming protein-protein interfaces. Finally, the amino acid frequencies for disordered proteins, computed during the development of the matrices, were compared with amino acid frequencies for different categories of secondary structure in ordered proteins. The highest correlations were observed between the amino acid frequencies in disordered proteins and the solvent-exposed loops and turns of ordered proteins, supporting an emerging structural model for disordered proteins.

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Scatter plot of the residue-normalized diagonal values, pii, for the eight secondary structure matrices and D85. The plot is ordered based upon increasing pii of the D85 matrix. Lines between data points from the same matrix are added for clarity. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.). D, disorder; O, order.
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fig6: Scatter plot of the residue-normalized diagonal values, pii, for the eight secondary structure matrices and D85. The plot is ordered based upon increasing pii of the D85 matrix. Lines between data points from the same matrix are added for clarity. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.). D, disorder; O, order.

Mentions: Previous studies have indicated that disordered proteins are evolving more rapidly than ordered proteins but a comparison has not been made between disordered proteins and the individual secondary structure classes of ordered proteins. Figure 6 shows a scatter plot of the pii values for the eight secondary structure matrices developed by Goldman et al. (1998) and the D85 matrix developed in this study. The plot is ordered based upon increasing pii values of the D85 matrix. Lines between data points from the same matrix are added for clarity. From this figure, it is clear that the buried residues from ordered proteins are the most conserved and the disordered residues are the least conserved, even at 85–100% identity. Each amino acid in disordered proteins is less conserved than it's counterpart in ordered proteins except tryptophan in exposed turns and coils and glycine in exposed helices. This result suggests that the evolution of disordered proteins is more neutral or less prone to purifying selection than ordered proteins.


Comparing models of evolution for ordered and disordered proteins.

Brown CJ, Johnson AK, Daughdrill GW - Mol. Biol. Evol. (2009)

Scatter plot of the residue-normalized diagonal values, pii, for the eight secondary structure matrices and D85. The plot is ordered based upon increasing pii of the D85 matrix. Lines between data points from the same matrix are added for clarity. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.). D, disorder; O, order.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822292&req=5

fig6: Scatter plot of the residue-normalized diagonal values, pii, for the eight secondary structure matrices and D85. The plot is ordered based upon increasing pii of the D85 matrix. Lines between data points from the same matrix are added for clarity. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.). D, disorder; O, order.
Mentions: Previous studies have indicated that disordered proteins are evolving more rapidly than ordered proteins but a comparison has not been made between disordered proteins and the individual secondary structure classes of ordered proteins. Figure 6 shows a scatter plot of the pii values for the eight secondary structure matrices developed by Goldman et al. (1998) and the D85 matrix developed in this study. The plot is ordered based upon increasing pii values of the D85 matrix. Lines between data points from the same matrix are added for clarity. From this figure, it is clear that the buried residues from ordered proteins are the most conserved and the disordered residues are the least conserved, even at 85–100% identity. Each amino acid in disordered proteins is less conserved than it's counterpart in ordered proteins except tryptophan in exposed turns and coils and glycine in exposed helices. This result suggests that the evolution of disordered proteins is more neutral or less prone to purifying selection than ordered proteins.

Bottom Line: Disordered proteins do not typically maintain long-range interactions, so the constraints on their evolution should be different than ordered proteins.Glutamic acid and asparagine were interesting exceptions to this result.Finally, the amino acid frequencies for disordered proteins, computed during the development of the matrices, were compared with amino acid frequencies for different categories of secondary structure in ordered proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Idaho, USA. celesteb@uidaho.edu

ABSTRACT
Most models of protein evolution are based upon proteins that form relatively rigid 3D structures. A significant fraction of proteins, the so-called disordered proteins, do not form rigid 3D structures and sample a broad conformational ensemble. Disordered proteins do not typically maintain long-range interactions, so the constraints on their evolution should be different than ordered proteins. To test this hypothesis, we developed and compared models of evolution for disordered and ordered proteins. Substitution matrices were constructed using the sequences of putative homologs for sets of experimentally characterized disordered and ordered proteins. Separate matrices, at three levels of sequence similarity (>85%, 85-60%, and 60-40%), were inferred for each type of protein structure. The substitution matrices for disordered and ordered proteins differed significantly at each level of sequence similarity. The disordered matrices reflected a greater likelihood of evolutionary changes, relative to the ordered matrices, and these changes involved nonconservative substitutions. Glutamic acid and asparagine were interesting exceptions to this result. Important differences between the substitutions that are accepted in disordered proteins relative to ordered proteins were also identified. In general, disordered proteins have fewer evolutionary constraints than ordered proteins. However, some residues like tryptophan and tyrosine are highly conserved in disordered proteins. This is due to their important role in forming protein-protein interfaces. Finally, the amino acid frequencies for disordered proteins, computed during the development of the matrices, were compared with amino acid frequencies for different categories of secondary structure in ordered proteins. The highest correlations were observed between the amino acid frequencies in disordered proteins and the solvent-exposed loops and turns of ordered proteins, supporting an emerging structural model for disordered proteins.

Show MeSH
Related in: MedlinePlus