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Relative Stabilities of Conserved and Non-Conserved Structures in the OB-Fold Superfamily
AbstractThe OB-fold is a diverse structure superfamily based on a β-barrel motif that is often supplemented with additional non-conserved secondary structures. Previous deletion mutagenesis and NMR hydrogen exchange studies of three OB-fold proteins showed that the structural stabilities of sites within the conserved β-barrels were larger than sites in non-conserved segments. In this work we examined a database of 80 representative domain structures currently classified as OB-folds, to establish the basis of this effect. Residue-specific values were obtained for the number of Cα-Cα distance contacts, sequence hydrophobicities, crystallographic B-factors, and theoretical B-factors calculated from a Gaussian Network Model. All four parameters point to a larger average flexibility for the non-conserved structures compared to the conserved β-barrels. The theoretical B-factors and contact densities show the highest sensitivity.Our results suggest a model of protein structure evolution in which novel structural features develop at the periphery of conserved motifs. Core residues are more resistant to structural changes during evolution since their substitution would disrupt a larger number of interactions. Similar factors are likely to account for the differences in stability to unfolding between conserved and non-conserved structures.
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Guardino, K.M.; Sheftic, S.R.; Slattery, R.E.; Alexandrescu, A.T. Relative Stabilities of Conserved and Non-Conserved Structures in the OB-Fold Superfamily. Int. J. Mol. Sci. 2009, 10, 2412-2430.View more citation formats
Guardino KM, Sheftic SR, Slattery RE, Alexandrescu AT. Relative Stabilities of Conserved and Non-Conserved Structures in the OB-Fold Superfamily. International Journal of Molecular Sciences. 2009; 10(5):2412-2430.Chicago/Turabian Style
Guardino, Kaitlyn M.; Sheftic, Sarah R.; Slattery, Robert E.; Alexandrescu, Andrei T. 2009. "Relative Stabilities of Conserved and Non-Conserved Structures in the OB-Fold Superfamily." Int. J. Mol. Sci. 10, no. 5: 2412-2430.