Nature 367, 660 - 663 (17 February 1994); doi:10.1038/367660a0

Measurement of the -sheet-forming propensities of amino acids

Daniel L. Minor Jr^* & Peter S. Kim^†

Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Departments of ^*Chemistry and ^†Biology, Massachusetts Institute of Technology, Nine Cambridge Centre, Cambridge, Massachusetts 02142, USA

SEVERAL model systems have been used to evaluate the -helical propensities of different amino acids^1–7. In contrast, experimental quantitation of -sheet preferences has been addressed in only one model system, a zinc-finger peptide⁸. Here we measure the relative propensity for -sheet formation of the twenty naturally occurring amino acids in a variant of the small, monomeric, -sheet-rich, IgG-binding domain from protein G. Amino-acid substitutions were made at a guest site on the solvent-exposed surface of the -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 -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 -sheet preferences can be important determinants of protein stability.

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