Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions. / Iešmantavičius, Vytautas; Jensen, Malene Ringkjøbing; Ozenne, Valéry; Blackledge, Martin; Poulsen, Flemming Martin; Kjærgaard, Magnus.

I: Journal of the American Chemical Society, Bind 135, Nr. 27, 10.07.2013, s. 10155-63.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Iešmantavičius, V, Jensen, MR, Ozenne, V, Blackledge, M, Poulsen, FM & Kjærgaard, M 2013, 'Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions', Journal of the American Chemical Society, bind 135, nr. 27, s. 10155-63. https://doi.org/10.1021/ja4045532

APA

Iešmantavičius, V., Jensen, M. R., Ozenne, V., Blackledge, M., Poulsen, F. M., & Kjærgaard, M. (2013). Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions. Journal of the American Chemical Society, 135(27), 10155-63. https://doi.org/10.1021/ja4045532

CBE

Iešmantavičius V, Jensen MR, Ozenne V, Blackledge M, Poulsen FM, Kjærgaard M. 2013. Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions. Journal of the American Chemical Society. 135(27):10155-63. https://doi.org/10.1021/ja4045532

MLA

Vancouver

Iešmantavičius V, Jensen MR, Ozenne V, Blackledge M, Poulsen FM, Kjærgaard M. Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions. Journal of the American Chemical Society. 2013 jul 10;135(27):10155-63. https://doi.org/10.1021/ja4045532

Author

Iešmantavičius, Vytautas ; Jensen, Malene Ringkjøbing ; Ozenne, Valéry ; Blackledge, Martin ; Poulsen, Flemming Martin ; Kjærgaard, Magnus. / Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions. I: Journal of the American Chemical Society. 2013 ; Bind 135, Nr. 27. s. 10155-63.

Bibtex

@article{202956c3935b4d9085b0f0084ba6ce88,
title = "Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions",
abstract = "Intrinsically disordered proteins (IDPs) are widespread and important in biology but defy the classical protein structure-function paradigm by being functional in the absence of a stable, folded conformation. Here we investigate the coupling between transient secondary and tertiary structure in the protein activator for thyroid hormone and retinoid receptors (ACTR) by rationally modulating the helical propensity of a partially formed α-helix via mutations. Eight mutations predicted to affect the population of a transient helix were produced and investigated by NMR spectroscopy. Chemical shift changes distant to the mutation site are observed in regions containing other transient helices indicating that distant helices are stabilized through long-range hydrophobic helix-helix interactions and demonstrating the coupling of transient secondary and tertiary structure. The long-range structure of ACTR is also probed using paramagnetic relaxation enhancements (PRE) and residual dipolar couplings, which reveal an additional long-range contact between the N- and C-terminal segments. Compared to residual dipolar couplings and PRE, modulation of the helical propensity by mutagenesis thus reveals a different set of long-range interactions that may be obscured by stronger interactions that dominate other NMR measurements. This approach thus offers a complementary and generally applicable strategy for probing long-range structure in disordered proteins.",
keywords = "Intrinsically Disordered Proteins, Models, Molecular, Protein Conformation",
author = "Vytautas Ie{\v s}mantavi{\v c}ius and Jensen, {Malene Ringkj{\o}bing} and Val{\'e}ry Ozenne and Martin Blackledge and Poulsen, {Flemming Martin} and Magnus Kj{\ae}rgaard",
year = "2013",
month = jul,
day = "10",
doi = "10.1021/ja4045532",
language = "English",
volume = "135",
pages = "10155--63",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",
number = "27",

}

RIS

TY - JOUR

T1 - Modulation of the intrinsic helix propensity of an intrinsically disordered protein reveals long-range helix-helix interactions

AU - Iešmantavičius, Vytautas

AU - Jensen, Malene Ringkjøbing

AU - Ozenne, Valéry

AU - Blackledge, Martin

AU - Poulsen, Flemming Martin

AU - Kjærgaard, Magnus

PY - 2013/7/10

Y1 - 2013/7/10

N2 - Intrinsically disordered proteins (IDPs) are widespread and important in biology but defy the classical protein structure-function paradigm by being functional in the absence of a stable, folded conformation. Here we investigate the coupling between transient secondary and tertiary structure in the protein activator for thyroid hormone and retinoid receptors (ACTR) by rationally modulating the helical propensity of a partially formed α-helix via mutations. Eight mutations predicted to affect the population of a transient helix were produced and investigated by NMR spectroscopy. Chemical shift changes distant to the mutation site are observed in regions containing other transient helices indicating that distant helices are stabilized through long-range hydrophobic helix-helix interactions and demonstrating the coupling of transient secondary and tertiary structure. The long-range structure of ACTR is also probed using paramagnetic relaxation enhancements (PRE) and residual dipolar couplings, which reveal an additional long-range contact between the N- and C-terminal segments. Compared to residual dipolar couplings and PRE, modulation of the helical propensity by mutagenesis thus reveals a different set of long-range interactions that may be obscured by stronger interactions that dominate other NMR measurements. This approach thus offers a complementary and generally applicable strategy for probing long-range structure in disordered proteins.

AB - Intrinsically disordered proteins (IDPs) are widespread and important in biology but defy the classical protein structure-function paradigm by being functional in the absence of a stable, folded conformation. Here we investigate the coupling between transient secondary and tertiary structure in the protein activator for thyroid hormone and retinoid receptors (ACTR) by rationally modulating the helical propensity of a partially formed α-helix via mutations. Eight mutations predicted to affect the population of a transient helix were produced and investigated by NMR spectroscopy. Chemical shift changes distant to the mutation site are observed in regions containing other transient helices indicating that distant helices are stabilized through long-range hydrophobic helix-helix interactions and demonstrating the coupling of transient secondary and tertiary structure. The long-range structure of ACTR is also probed using paramagnetic relaxation enhancements (PRE) and residual dipolar couplings, which reveal an additional long-range contact between the N- and C-terminal segments. Compared to residual dipolar couplings and PRE, modulation of the helical propensity by mutagenesis thus reveals a different set of long-range interactions that may be obscured by stronger interactions that dominate other NMR measurements. This approach thus offers a complementary and generally applicable strategy for probing long-range structure in disordered proteins.

KW - Intrinsically Disordered Proteins

KW - Models, Molecular

KW - Protein Conformation

U2 - 10.1021/ja4045532

DO - 10.1021/ja4045532

M3 - Journal article

C2 - 23758617

VL - 135

SP - 10155

EP - 10163

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 27

ER -