Toward protein NMR at physiological concentrations by
hyperpolarized water-Finding and mapping uncharted
conformational spaces

J 2022

Toward protein NMR at physiological concentrations by hyperpolarized water-Finding and mapping uncharted conformational spaces

EPASTO, Ludovica M., Kateryna CHE, Fanny KOZAK, Albina SELIMOVIC, Pavel KADEŘÁVEK et. al.

Basic information

Original name

Toward protein NMR at physiological concentrations by hyperpolarized water-Finding and mapping uncharted conformational spaces

Authors

EPASTO, Ludovica M., Kateryna CHE, Fanny KOZAK, Albina SELIMOVIC, Pavel KADEŘÁVEK (203 Czech Republic, guarantor, belonging to the institution) and Dennis KURZBACH

Edition

Science advances, New York, American Association for the Advancement of Science, 2022, 2375-2548

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 13.600

RIV identification code

RIV/00216224:14740/22:00126458

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1126/sciadv.abq5179

UT WoS

000836990600040

Keywords in English

DYNAMIC NUCLEAR-POLARIZATIONINTRINSICALLY DISORDERED PROTEINSTRANSCRIPTION FACTORSDNAMAXMYCPREDICTIONMECHANISMINSIGHTSCOGNATE

Abstract

V originále

Nuclear magnetic resonance (NMR) spectroscopy is a key method for determining the structural dynamics of proteins in their native solution state. However, the low sensitivity of NMR typically necessitates nonphysiologically high sample concentrations, which often limit the relevance of the recorded data. We show how to use hyperpolarized water by dissolution dynamic nuclear polarization (DDNP) to acquire protein spectra at concentrations of 1.M within seconds and with a high signal-to-noise ratio. The importance of approaching physiological concentrations is demonstrated for the vital MYC-associated factor X, which we show to switch conformations when diluted. While in vitro conditions lead to a population of the well-documented dimer, concentrations lowered by more than two orders of magnitude entail dimer dissociation and formation of a globularly folded monomer. We identified this structure by integrating DDNP with computational techniques to overcome the often-encountered constraint of DDNP of limited structural information provided by the typically detected one-dimensional spectra.

Links

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

EPASTO, Ludovica M., Kateryna CHE, Fanny KOZAK, Albina SELIMOVIC, Pavel KADEŘÁVEK and Dennis KURZBACH. Toward protein NMR at physiological concentrations by hyperpolarized water-Finding and mapping uncharted conformational spaces. Science advances. New York: American Association for the Advancement of Science, 2022, vol. 8, No 31, p. 1-7. ISSN 2375-2548. Available from: https://dx.doi.org/10.1126/sciadv.abq5179.

@article{2212033,
   author = {Epasto, Ludovica M. and Che, Kateryna and Kozak, Fanny and Selimovic, Albina and Kadeřávek, Pavel and Kurzbach, Dennis},
   article_location = {New York},
   article_number = {31},
   doi = {http://dx.doi.org/10.1126/sciadv.abq5179},
   keywords = {DYNAMIC NUCLEAR-POLARIZATIONINTRINSICALLY DISORDERED PROTEINSTRANSCRIPTION FACTORSDNAMAXMYCPREDICTIONMECHANISMINSIGHTSCOGNATE},
   language = {eng},
   issn = {2375-2548},
   journal = {Science advances},
   title = {Toward protein NMR at physiological concentrations by hyperpolarized water-Finding and mapping uncharted conformational spaces},
   url = {https://www.science.org/doi/10.1126/sciadv.abq5179},
   volume = {8},
   year = {2022}
}

TY  - JOUR
ID  - 2212033
AU  - Epasto, Ludovica M. - Che, Kateryna - Kozak, Fanny - Selimovic, Albina - Kadeřávek, Pavel - Kurzbach, Dennis
PY  - 2022
TI  - Toward protein NMR at physiological concentrations by hyperpolarized water-Finding and mapping uncharted conformational spaces
JF  - Science advances
VL  - 8
IS  - 31
SP  - 1-7
EP  - 1-7
PB  - American Association for the Advancement of Science
SN  - 23752548
KW  - DYNAMIC NUCLEAR-POLARIZATIONINTRINSICALLY DISORDERED PROTEINSTRANSCRIPTION FACTORSDNAMAXMYCPREDICTIONMECHANISMINSIGHTSCOGNATE
UR  - https://www.science.org/doi/10.1126/sciadv.abq5179
N2  - Nuclear magnetic resonance (NMR) spectroscopy is a key method for determining the structural dynamics of proteins in their native solution state. However, the low sensitivity of NMR typically necessitates nonphysiologically high sample concentrations, which often limit the relevance of the recorded data. We show how to use hyperpolarized water by dissolution dynamic nuclear polarization (DDNP) to acquire protein spectra at concentrations of 1.M within seconds and with a high signal-to-noise ratio. The importance of approaching physiological concentrations is demonstrated for the vital MYC-associated factor X, which we show to switch conformations when diluted. While in vitro conditions lead to a population of the well-documented dimer, concentrations lowered by more than two orders of magnitude entail dimer dissociation and formation of a globularly folded monomer. We identified this structure by integrating DDNP with computational techniques to overcome the often-encountered constraint of DDNP of limited structural information provided by the typically detected one-dimensional spectra.
ER  -

EPASTO, Ludovica M., Kateryna CHE, Fanny KOZAK, Albina SELIMOVIC, Pavel KADEŘÁVEK and Dennis KURZBACH. Toward protein NMR at physiological concentrations by hyperpolarized water-Finding and mapping uncharted conformational spaces. \textit{Science advances}. New York: American Association for the Advancement of Science, 2022, vol.~8, No~31, p.~1-7. ISSN~2375-2548. Available from: https://dx.doi.org/10.1126/sciadv.abq5179.

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