Abstract
THE molten globule is a compact protein conformation that has a secondary structure content like that of the native protein, but poorly defined tertiary structure. It is a stable state for a few proteins under particular conditions1 and could be a ubiquitous kinetic intermediate in protein folding2. The extent to which native interactions, above the level of the secondary structure, are preserved in this conformation is not so far known. Here we report that α-lactalbumin can adopt a molten globule conformation when one of its four disulphide bonds is reduced. In this state, the three other disulphide bonds rearrange spontaneously, at the same rate as when the protein is fully unfolded, to a number of different disulphide bond isomers that tend to maintain the molten globule conformation. That the molten globule state is compatible with a variety of disulphide bond pairings suggests that it is unlikely to be stabilized by many specific tertiary interactions.
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Ewbank, J., Creighton, T. The molten globule protein conformation probed by disulphide bonds. Nature 350, 518–520 (1991). https://doi.org/10.1038/350518a0
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DOI: https://doi.org/10.1038/350518a0
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