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Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination
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SYSNO ASEP 0485552 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination Author(s) Konte, N.D. (CH)
Krepl, Miroslav (BFU-R) ORCID
Damberger, F.F. (CH)
Ripin, N. (CH)
Duss, O. (US)
Šponer, Jiří (BFU-R) RID, ORCID
Allain, F.H.T. (CH)Number of authors 7 Article number 654 Source Title Nature Communications. - : Nature Publishing Group
Roč. 8, SEP2017 (2017)Number of pages 12 s. Publication form Online - E Language eng - English Country GB - United Kingdom Keywords nmr structure determination ; particle mesh ewald Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GBP305/12/G034 GA ČR - Czech Science Foundation (CSF) Institutional support BFU-R - RVO:68081707 UT WOS 000411416100014 DOI 10.1038/s41467-017-00631-3 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2018
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