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Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469821/ https://www.ncbi.nlm.nih.gov/pubmed/22917971 http://dx.doi.org/10.1016/j.jmb.2012.08.003 |
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author | Wensley, Beth G. Kwa, Lee Gyan Shammas, Sarah L. Rogers, Joseph M. Clarke, Jane |
author_facet | Wensley, Beth G. Kwa, Lee Gyan Shammas, Sarah L. Rogers, Joseph M. Clarke, Jane |
author_sort | Wensley, Beth G. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3469821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-34698212012-11-14 Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness Wensley, Beth G. Kwa, Lee Gyan Shammas, Sarah L. Rogers, Joseph M. Clarke, Jane J Mol Biol Article 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. Elsevier 2012-10-26 /pmc/articles/PMC3469821/ /pubmed/22917971 http://dx.doi.org/10.1016/j.jmb.2012.08.003 Text en © 2012 Elsevier Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Wensley, Beth G. Kwa, Lee Gyan Shammas, Sarah L. Rogers, Joseph M. Clarke, Jane Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness |
title | Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness |
title_full | Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness |
title_fullStr | Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness |
title_full_unstemmed | Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness |
title_short | Protein Folding: Adding a Nucleus to Guide Helix Docking Reduces Landscape Roughness |
title_sort | protein folding: adding a nucleus to guide helix docking reduces landscape roughness |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469821/ https://www.ncbi.nlm.nih.gov/pubmed/22917971 http://dx.doi.org/10.1016/j.jmb.2012.08.003 |
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