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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F22%3A00126458" target="_blank" >RIV/00216224:14740/22:00126458 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.science.org/doi/10.1126/sciadv.abq5179" target="_blank" >https://www.science.org/doi/10.1126/sciadv.abq5179</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/sciadv.abq5179" target="_blank" >10.1126/sciadv.abq5179</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Science advances

ISSN

2375-2548

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

31

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

1-7

Kód UT WoS článku

000836990600040

EID výsledku v databázi Scopus

2-s2.0-85135462122