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Contribution of hydrophobic interactions to protein stability

Nature volume 333, pages 784–786 (1988)Cite this article

Abstract

A major factor in the folding of proteins is the burying of hydro-phobic side chains. A specific example is the packing of α-helices on β-sheets by interdigitation of nonpolar side chains. The contri-butions of these interactions to the energetics of protein stability may be measured by simple protein engineering experiments. We have used site-directed mutagenesis to truncate hydrophobic side chains at an α -helix/ β-sheet interface in the small ribonuclease from Bacillus amyloliquefadens (barnase). The decreases in stabil-ity of the mutant proteins were measured by their susceptibility to urea denaturation. Creation of a cavity the size of a –CH2–group destabilizes the enzyme by 1.1 kcal mol−1, and a cavity the size of three such groups by 4.0 kcal mol−1.

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Authors and Affiliations

  1. Department of Chemistry, Imperial College of Science and Technology, London, SW7 2AZ, UK

    James T. Kellis Jr, Kerstin Nyberg, Das̆a S˘ail & Alan R. Fersht

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  1. James T. Kellis Jr
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  2. Kerstin Nyberg
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  3. Das̆a S˘ail
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  4. Alan R. Fersht
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Kellis, J., Nyberg, K., S˘ail, D. et al. Contribution of hydrophobic interactions to protein stability. Nature 333, 784–786 (1988). https://doi.org/10.1038/333784a0

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