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Protein Sci. 2004 Apr;13(4):958-70.

Intermediates and the folding of proteins L and G.

Author information

1
Department of Bioengineering, 472 Donner Laboratory, University of California, Berkeley, Berkeley, CA 94720-1762, USA.

Abstract

We use a minimalist protein model, in combination with a sequence design strategy, to determine differences in primary structure for proteins L and G, which 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.

PMID:
15044729
PMCID:
PMC2280051
DOI:
10.1110/ps.03316004
[Indexed for MEDLINE]
Free PMC Article

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