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Proline scanning mutagenesis of a molten globule reveals non-cooperative formation of a protein's overall topology

Nature Structural Biology volume 3, pages 682–687 (1996)Cite this article

Abstract

Small proteins generally fold cooperatively: disruption of significant parts of the folded structure leads to unfolding of the rest of the protein. We show here, using proline scanning mutagenesis, that the native-like tertiary fold of the α-lactalbumin (α-LA) molten globule is formed by the non-cooperative assembly of its constituent helices. In contrast to the drastic destabilizing effects of proline substitutions in cooperatively folded proteins, proline mutations in the molten globule appear to cause only individual helices to unfold, without significantly influencing the other helices or the overall topology. Thus, the key determinants of a protein's overall fold may not be of the all-or-none type.

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Author notes

  1. Brenda A. Schulman

    Present address: Laboratory of Molecular Oncology Building 149, Massachusetts General Hospital Cancer Center, 13th Street, Charlestown, Massachusetts, 02129, USA

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  1. Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Brenda A. Schulman & Peter S. Kim

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Schulman, B., Kim, P. Proline scanning mutagenesis of a molten globule reveals non-cooperative formation of a protein's overall topology. Nat Struct Mol Biol 3, 682–687 (1996). https://doi.org/10.1038/nsb0896-682

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