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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Journal of Molecular Biology, Vol. 423, No. 3, 26.10.2012, p. 273-283.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Wensley, BG, Kwa, LG, Shammas, SL, Rogers, JM & Clarke, J 2012, 'Protein folding: Adding a nucleus to guide helix docking reduces landscape roughness', Journal of Molecular Biology, vol. 423, no. 3, pp. 273-283. https://doi.org/10.1016/j.jmb.2012.08.003

APA

Wensley, B. G., Kwa, L. G., Shammas, S. L., Rogers, J. M., & Clarke, J. (2012). Protein folding: Adding a nucleus to guide helix docking reduces landscape roughness. Journal of Molecular Biology, 423(3), 273-283. https://doi.org/10.1016/j.jmb.2012.08.003

Vancouver

Wensley BG, Kwa LG, Shammas SL, Rogers JM, Clarke J. Protein folding: Adding a nucleus to guide helix docking reduces landscape roughness. Journal of Molecular Biology. 2012 Oct 26;423(3):273-283. https://doi.org/10.1016/j.jmb.2012.08.003

Author

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. In: Journal of Molecular Biology. 2012 ; Vol. 423, No. 3. pp. 273-283.

Bibtex

@article{08d37530dbba45fcb675264953a553d0,
title = "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.",
keywords = "energy landscape, helix bundle, minimal frustration, protein folding, Φ-value analysis",
author = "Wensley, {Beth G.} and Kwa, {Lee Gyan} and Shammas, {Sarah L.} and Rogers, {Joseph M.} and Jane Clarke",
year = "2012",
month = oct,
day = "26",
doi = "10.1016/j.jmb.2012.08.003",
language = "English",
volume = "423",
pages = "273--283",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press",
number = "3",

}

RIS

TY - JOUR

T1 - Protein folding

T2 - Adding a nucleus to guide helix docking reduces landscape roughness

AU - Wensley, Beth G.

AU - Kwa, Lee Gyan

AU - Shammas, Sarah L.

AU - Rogers, Joseph M.

AU - Clarke, Jane

PY - 2012/10/26

Y1 - 2012/10/26

N2 - 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.

AB - 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.

KW - energy landscape

KW - helix bundle

KW - minimal frustration

KW - protein folding

KW - Φ-value analysis

UR - http://www.scopus.com/inward/record.url?scp=84867080086&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2012.08.003

DO - 10.1016/j.jmb.2012.08.003

M3 - Journal article

C2 - 22917971

AN - SCOPUS:84867080086

VL - 423

SP - 273

EP - 283

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 3

ER -

ID: 244651454