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Measurement of the β-sheet-forming propensities of amino acids

Abstract

SEVERAL model systems have been used to evaluate the α-helical propensities of different amino acids1–7. In contrast, experimental quantitation of β-sheet preferences has been addressed in only one model system, a zinc-finger peptide8. Here we measure the relative propensity for β-sheet formation of the twenty naturally occurring amino acids in a variant of the small, monomeric, β-sheet-rich, IgG-binding domain from protein G. Amino-acid substitutions were made at a guest site on the solvent-exposed surface of the β-sheet. Several criteria were used to establish that the mutations did not cause significant structural changes: binding to the Fc domain of IgG, calorimetric unfolding and NMR spectroscopy. Characterization of the thermal stabilities of these proteins leads to a thermodynamic scale for β-sheet propensities that spans a range of 2 kcal mol−1 for the naturally occurring amino acids, excluding proline. The magnitude of the differences suggests that β-sheet preferences can be important determinants of protein stability.

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Minor, D., Kim, P. Measurement of the β-sheet-forming propensities of amino acids. Nature 367, 660–663 (1994). https://doi.org/10.1038/367660a0

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