Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00485552" target="_blank" >RIV/68081707:_____/17:00485552 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/17:73584447

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41467-017-00631-3" target="_blank" >http://dx.doi.org/10.1038/s41467-017-00631-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-017-00631-3" target="_blank" >10.1038/s41467-017-00631-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination

Popis výsledku v původním jazyce

The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3 ' untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5 '-UUUAA-3 ' originating from the COX-2 3 '-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high-or low-affinity binding with functional implications. This study highlights a mechanism for RNA discrimination possibly common to multiple RRMs as several prominent members display a similar rearrangement of aromatic residues upon binding their targets.

Název v anglickém jazyce

Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination

Popis výsledku anglicky

The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3 ' untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5 '-UUUAA-3 ' originating from the COX-2 3 '-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high-or low-affinity binding with functional implications. This study highlights a mechanism for RNA discrimination possibly common to multiple RRMs as several prominent members display a similar rearrangement of aromatic residues upon binding their targets.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

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Svazek periodika

8

Číslo periodika v rámci svazku

SEP2017

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

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Kód UT WoS článku

000411416100014

EID výsledku v databázi Scopus

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