Intermediates and the folding of proteins L and G
We use a minimalist protein model, in combination with a sequence design strategy, to determine differences in primary structure for proteins L and G that are responsible for the two proteins folding through distinctly different folding mechanisms. We find that the folding of proteins L and G are consistent with a nucleation-condensation mechanism, each of which is described as helix-assisted {beta}-1 and {beta}-2 hairpin formation, respectively. We determine that the model for protein G exhibits an early intermediate that precedes the rate-limiting barrier of folding and which draws together misaligned secondary structure elements that are stabilized by hydrophobic core contacts involving the third {beta}-strand, and presages the later transition state in which the correct strand alignment of these same secondary structure elements is restored. Finally the validity of the targeted intermediate ensemble for protein G was analyzed by fitting the kinetic data to a two-step first order reversible reaction, proving that protein G folding involves an on-pathway early intermediate, and should be populated and therefore observable by experiment.
- Research Organization:
- COLLABORATION - UCBerkeley
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 928331
- Report Number(s):
- LBNL-54633; R&D Project: 449801; BnR: KJ0101010; TRN: US200815%%845
- Journal Information:
- Protein Science, Vol. 13; Related Information: Journal Publication Date: 2004
- Country of Publication:
- United States
- Language:
- English
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