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Protein folding: adding a nucleus to guide helix docking reduces landscape roughness.

ABSTRACT: The elongated three-helix-bundle spectrin domains R16 and R17 fold and unfold unusually slowly over a rough energy landscape, in contrast to the homologue R15, which folds fast over a much smoother, more typical landscape. R15 folds via a nucleation-condensation mechanism that guides the docking of the A and C-helices. However, in R16 and R17, the secondary structure forms first and the two helices must then dock in the correct register. Here, we use variants of R16 and R17 to demonstrate that substitution of just five key residues is sufficient to alter the folding mechanism and reduce the landscape roughness. We suggest that, by providing access to an alternative, faster, folding route over their landscape, R16 and R17 can circumvent their slow, frustrated wild-type folding mechanism.

SUBMITTER: Wensley BG

PROVIDER: S-EPMC3469821 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Protein folding: adding a nucleus to guide helix docking reduces landscape roughness.

Wensley Beth G BG Kwa Lee Gyan LG Shammas Sarah L SL Rogers Joseph M JM Clarke Jane J

Journal of molecular biology 20120820 3

The elongated three-helix-bundle spectrin domains R16 and R17 fold and unfold unusually slowly over a rough energy landscape, in contrast to the homologue R15, which folds fast over a much smoother, more typical landscape. R15 folds via a nucleation-condensation mechanism that guides the docking of the A and C-helices. However, in R16 and R17, the secondary structure forms first and the two helices must then dock in the correct register. Here, we use variants of R16 and R17 to demonstrate that s ...[more]

PMID: 22917971

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