The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain

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Standard

The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain. / Pedersen, Søren W; Hultqvist, Greta; Strømgaard, Kristian; Jemth, Per.

In: PLOS ONE, Vol. 9, No. 4, e95619, 2014, p. 1-7.

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

Harvard

Pedersen, SW, Hultqvist, G, Strømgaard, K & Jemth, P 2014, 'The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain', PLOS ONE, vol. 9, no. 4, e95619, pp. 1-7. https://doi.org/10.1371/journal.pone.0095619

APA

Pedersen, S. W., Hultqvist, G., Strømgaard, K., & Jemth, P. (2014). The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain. PLOS ONE, 9(4), 1-7. [e95619]. https://doi.org/10.1371/journal.pone.0095619

Vancouver

Pedersen SW, Hultqvist G, Strømgaard K, Jemth P. The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain. PLOS ONE. 2014;9(4):1-7. e95619. https://doi.org/10.1371/journal.pone.0095619

Author

Pedersen, Søren W ; Hultqvist, Greta ; Strømgaard, Kristian ; Jemth, Per. / The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain. In: PLOS ONE. 2014 ; Vol. 9, No. 4. pp. 1-7.

Bibtex

@article{76f6679bc7174b2c8895f2fb9924487a,
title = "The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain",
abstract = "Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.",
author = "Pedersen, {S{\o}ren W} and Greta Hultqvist and Kristian Str{\o}mgaard and Per Jemth",
year = "2014",
doi = "10.1371/journal.pone.0095619",
language = "English",
volume = "9",
pages = "1--7",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

RIS

TY - JOUR

T1 - The role of backbone hydrogen bonds in the transition state for protein folding of a PDZ domain

AU - Pedersen, Søren W

AU - Hultqvist, Greta

AU - Strømgaard, Kristian

AU - Jemth, Per

PY - 2014

Y1 - 2014

N2 - Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.

AB - Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.

U2 - 10.1371/journal.pone.0095619

DO - 10.1371/journal.pone.0095619

M3 - Journal article

C2 - 24748272

VL - 9

SP - 1

EP - 7

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 4

M1 - e95619

ER -

ID: 108649759