1hd3
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A-SPECTRIN SH3 DOMAIN F52Y MUTANT
OverviewOverview
Here we present a method for determining the inference of non-native, conformations in the folding of a small domain, alpha-spectrin Src, homology 3 domain. This method relies on the preservation of all native, interactions after Tyr/Phe exchanges in solvent-exposed, contact-free, positions. Minor changes in solvent exposure and free energy of the, denatured ensemble are in agreement with the reverse hydrophobic effect, as the Tyr/Phe mutations slightly change the polypeptide, hydrophilic/hydrophobic balance. Interestingly, more important Gibbs, energy variations are observed in the transition state ensemble (TSE)., Considering the small changes induced by the H/OH replacements, the, observed energy variations in the TSE are rather notable, but of a, magnitude that would remain undetected under regular mutations that alter, the folded structure free energy. Hydrophobic residues outside of the, folding nucleus contribute to the stability of the TSE in an unspecific, nonlinear manner, producing a significant acceleration of both unfolding, and refolding rates, with little effect on stability. These results, suggest that sectors of the protein transiently reside in non-native areas, of the landscape during folding, with implications in the reading of phi, values from protein engineering experiments. Contrary to previous, proposals, the principle that emerges is that non-native contacts, or, conformations, could be beneficial in evolution and design of some fast, folding proteins.
About this StructureAbout this Structure
1HD3 is a Single protein structure of sequence from Gallus gallus with SO4 and GOL as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Unspecific hydrophobic stabilization of folding transition states., Viguera AR, Vega C, Serrano L, Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5349-54. PMID:11959988
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