Cold denaturation of a protein dimer monitored at atomic resolution

Mariusz Jaremko; Łukasz Jaremko; Hai Young Kim; Min Kyu Cho; Charles D. Schwieters; Karin Giller; Stefan Becker; Markus Zweckstetter

doi:10.1038/nchembio.1181

Cold denaturation of a protein dimer monitored at atomic resolution

Mariusz Jaremko, Łukasz Jaremko, Hai Young Kim, Min Kyu Cho, Charles D. Schwieters, Karin Giller, Stefan Becker, Markus Zweckstetter^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Protein folding and unfolding are crucial for a range of biological phenomena and human diseases. Defining the structural properties of the involved transient species is therefore of prime interest. Using a combination of cold denaturation with NMR spectroscopy, we reveal detailed insight into the unfolding of the homodimeric repressor protein CylR2. Seven three-dimensional structures of CylR2 at temperatures from 25 °C to -16 °C reveal a progressive dissociation of the dimeric protein into a native-like monomeric intermediate followed by transition into a highly dynamic, partially folded state. The core of the partially folded state seems critical for biological function and misfolding.

Original language	English (US)
Pages (from-to)	264-270
Number of pages	7
Journal	Nature Chemical Biology
Volume	9
Issue number	4
DOIs	https://doi.org/10.1038/nchembio.1181
State	Published - Apr 2013
Externally published	Yes

Bibliographical note

Funding Information:
We thank N. Rezaei-Ghaleh for useful discussions. This work was supported by the START and Ventures Programmes of Foundation for Polish Science (Fundacja na rzecz Nauki Polskiej; http://www.fnp.org.pl/) operated within the Innovative Economy Operational Programme (IE OP) 2007-2013 within European Regional Development Fund (L.J. and M.J.), the Iuventus Plus project no. IP2011 019471 from Polish Ministry of Sciences and Higher Education (M.J.) and the Cluster of Excellence and Deutsche Forschungsgemeinschaft Research Center “Nanoscale Microscopy and Molecular Physiology of the Brain” (to M.Z.). C.D.S. was supported by the Intramural Research Program of the Center for Information Technology at the US National Institutes of Health.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nchembio.1181

Cite this

@article{3e0d57e33cac45288e1ff1efdaf22737,

title = "Cold denaturation of a protein dimer monitored at atomic resolution",

abstract = "Protein folding and unfolding are crucial for a range of biological phenomena and human diseases. Defining the structural properties of the involved transient species is therefore of prime interest. Using a combination of cold denaturation with NMR spectroscopy, we reveal detailed insight into the unfolding of the homodimeric repressor protein CylR2. Seven three-dimensional structures of CylR2 at temperatures from 25 °C to -16 °C reveal a progressive dissociation of the dimeric protein into a native-like monomeric intermediate followed by transition into a highly dynamic, partially folded state. The core of the partially folded state seems critical for biological function and misfolding.",

author = "Mariusz Jaremko and {\L}ukasz Jaremko and Kim, {Hai Young} and Cho, {Min Kyu} and Schwieters, {Charles D.} and Karin Giller and Stefan Becker and Markus Zweckstetter",

note = "Funding Information: We thank N. Rezaei-Ghaleh for useful discussions. This work was supported by the START and Ventures Programmes of Foundation for Polish Science (Fundacja na rzecz Nauki Polskiej; http://www.fnp.org.pl/) operated within the Innovative Economy Operational Programme (IE OP) 2007-2013 within European Regional Development Fund (L.J. and M.J.), the Iuventus Plus project no. IP2011 019471 from Polish Ministry of Sciences and Higher Education (M.J.) and the Cluster of Excellence and Deutsche Forschungsgemeinschaft Research Center “Nanoscale Microscopy and Molecular Physiology of the Brain” (to M.Z.). C.D.S. was supported by the Intramural Research Program of the Center for Information Technology at the US National Institutes of Health.",

year = "2013",

month = apr,

doi = "10.1038/nchembio.1181",

language = "English (US)",

volume = "9",

pages = "264--270",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - Cold denaturation of a protein dimer monitored at atomic resolution

AU - Jaremko, Mariusz

AU - Jaremko, Łukasz

AU - Kim, Hai Young

AU - Cho, Min Kyu

AU - Schwieters, Charles D.

AU - Giller, Karin

AU - Becker, Stefan

AU - Zweckstetter, Markus

N1 - Funding Information: We thank N. Rezaei-Ghaleh for useful discussions. This work was supported by the START and Ventures Programmes of Foundation for Polish Science (Fundacja na rzecz Nauki Polskiej; http://www.fnp.org.pl/) operated within the Innovative Economy Operational Programme (IE OP) 2007-2013 within European Regional Development Fund (L.J. and M.J.), the Iuventus Plus project no. IP2011 019471 from Polish Ministry of Sciences and Higher Education (M.J.) and the Cluster of Excellence and Deutsche Forschungsgemeinschaft Research Center “Nanoscale Microscopy and Molecular Physiology of the Brain” (to M.Z.). C.D.S. was supported by the Intramural Research Program of the Center for Information Technology at the US National Institutes of Health.

PY - 2013/4

Y1 - 2013/4

N2 - Protein folding and unfolding are crucial for a range of biological phenomena and human diseases. Defining the structural properties of the involved transient species is therefore of prime interest. Using a combination of cold denaturation with NMR spectroscopy, we reveal detailed insight into the unfolding of the homodimeric repressor protein CylR2. Seven three-dimensional structures of CylR2 at temperatures from 25 °C to -16 °C reveal a progressive dissociation of the dimeric protein into a native-like monomeric intermediate followed by transition into a highly dynamic, partially folded state. The core of the partially folded state seems critical for biological function and misfolding.

AB - Protein folding and unfolding are crucial for a range of biological phenomena and human diseases. Defining the structural properties of the involved transient species is therefore of prime interest. Using a combination of cold denaturation with NMR spectroscopy, we reveal detailed insight into the unfolding of the homodimeric repressor protein CylR2. Seven three-dimensional structures of CylR2 at temperatures from 25 °C to -16 °C reveal a progressive dissociation of the dimeric protein into a native-like monomeric intermediate followed by transition into a highly dynamic, partially folded state. The core of the partially folded state seems critical for biological function and misfolding.

UR - http://www.scopus.com/inward/record.url?scp=84875442036&partnerID=8YFLogxK

U2 - 10.1038/nchembio.1181

DO - 10.1038/nchembio.1181

M3 - Article

C2 - 23396077

AN - SCOPUS:84875442036

SN - 1552-4450

VL - 9

SP - 264

EP - 270

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 4

ER -

Cold denaturation of a protein dimer monitored at atomic resolution

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this