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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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Frequencies of amino acids in disordered proteins are most similar to the frequencies of amino acids in the exposed coils and turns of ordered proteins. The line indicates a one-to-one correspondence between frequency in order and disorder. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.)
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fig5: Frequencies of amino acids in disordered proteins are most similar to the frequencies of amino acids in the exposed coils and turns of ordered proteins. The line indicates a one-to-one correspondence between frequency in order and disorder. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.)

Mentions: To investigate this possibility, the amino acid frequencies for the D85 matrix were compared with the frequencies identified by Goldman et al. (Goldman et al. 1998) for their eight structural classes of ordered proteins, buried or exposed alpha helices, beta sheets, turns (including bends) and coils. Table 4 shows that the amino acid frequencies for D85 are most highly correlated with those for the solvent-exposed coils and turns of ordered proteins. Figure 5 shows the correlation plot for the frequencies of individual amino acids from the solvent-exposed coils and turns of ordered proteins versus the amino acid frequencies from the D85 matrix. This strong correlation is important because it suggests that the evolution of coils and turns, which are the most structurally dynamic regions of ordered proteins, is most similar to the evolution of disordered proteins. If this is correct, it supports the assumption that the structural ensembles are similar.


Comparing models of evolution for ordered and disordered proteins.

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

Frequencies of amino acids in disordered proteins are most similar to the frequencies of amino acids in the exposed coils and turns of ordered proteins. The line indicates a one-to-one correspondence between frequency in order and disorder. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Frequencies of amino acids in disordered proteins are most similar to the frequencies of amino acids in the exposed coils and turns of ordered proteins. The line indicates a one-to-one correspondence between frequency in order and disorder. (Information for disordered proteins is based upon the >85% similarity matrix and for ordered proteins is from Goldman et al. 1998.)
Mentions: To investigate this possibility, the amino acid frequencies for the D85 matrix were compared with the frequencies identified by Goldman et al. (Goldman et al. 1998) for their eight structural classes of ordered proteins, buried or exposed alpha helices, beta sheets, turns (including bends) and coils. Table 4 shows that the amino acid frequencies for D85 are most highly correlated with those for the solvent-exposed coils and turns of ordered proteins. Figure 5 shows the correlation plot for the frequencies of individual amino acids from the solvent-exposed coils and turns of ordered proteins versus the amino acid frequencies from the D85 matrix. This strong correlation is important because it suggests that the evolution of coils and turns, which are the most structurally dynamic regions of ordered proteins, is most similar to the evolution of disordered proteins. If this is correct, it supports the assumption that the structural ensembles are similar.

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