Impact of an easily reducible disulfide bond on the oxidative folding rate of multi-disulfide-containing proteins

Authors: H.J. Leung; G. Xu; M. Narayan; H.A. Scheraga

Source: Journal of Peptide Research, Volume 65, Number 1, January 2005 , pp. 47-54(8)

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Abstract:

The burial of native disulfide bonds, formed within stable structure in the regeneration of multi-disulfide-containing proteins from their fully reduced states, is a key step in the folding process, as the burial greatly accelerates the oxidative folding rate of the protein by sequestering the native disulfide bonds from thiol-disulfide exchange reactions. Nevertheless, several proteins retain solvent-exposed disulfide bonds in their native structures. Here, we have examined the impact of an easily reducible native disulfide bond on the oxidative folding rate of a protein. Our studies reveal that the susceptibility of the (40–95) disulfide bond of Y92G bovine pancreatic ribonuclease A (RNase A) to reduction results in a reduced rate of oxidative regeneration, compared with wild-type RNase A. In the native state of RNase A, Tyr 92 lies atop its (40–95) disulfide bond, effectively shielding this bond from the reducing agent, thereby promoting protein oxidative regeneration. Our work sheds light on the unique contribution of a local structural element in promoting the oxidative folding of a multi-disulfide-containing protein.

Keywords: disulfide bond burial; easily reducible disulfide; native structure; oxidative folding; redox reagent; reductive unfolding

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1399-3011.2004.00189.x

Publication date: 2005-01-01