Sequence Reversal Prevents Chain Collapse and Yields Heat-Sensitive Intrinsic Disorder

Biophysical Journal
Lance R EnglishSteven T Whitten

Abstract

Sequence patterns of charge, hydrophobicity, hydrogen bonding, and other amino acid physicochemical properties contribute to mechanisms of protein folding, but how sequence composition and patterns influence the conformational dynamics of the denatured state ensemble is not fully understood. To investigate structure-sequence relationships in the denatured state, we reversed the sequence of staphylococcal nuclease and characterized its structure, thermodynamic character, and hydrodynamic radius using circular dichroism spectroscopy, dynamic light scattering, analytical ultracentrifugation, and size-exclusion chromatography as a function of temperature. The macromolecular size of "Retro-nuclease" is highly expanded in solution with characteristics similar to biological intrinsically disordered proteins. In contradistinction to a disordered state, Retro-nuclease exhibits a broad sigmoid transition of its hydrodynamic dimensions as temperature is increased, indicating a thermodynamically controlled compaction. Counterintuitively, the magnitude of these temperature-induced hydrodynamic changes exceed that observed from thermal denaturation of folded unaltered staphylococcal nuclease. Undetectable by calorimetry and intrinsic tryptop...Continue Reading

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Citations

Feb 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elisia A PaizSteven T Whitten
Jul 3, 2019·Entropy·Jiří VymětalKlára Hlouchová
Nov 5, 2019·The Journal of Physical Chemistry. B·Lance R EnglishSteven T Whitten

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