Recognition of N6-Methyladenosine by the YTHDC1 YTH Domain Studied by Molecular Dynamics and NMR Spectroscopy: The Role of Hydration
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00554790" target="_blank" >RIV/68081707:_____/21:00554790 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15640/21:73611186 RIV/00216224:14310/21:00122232
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jpcb.1c03541" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jpcb.1c03541</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jpcb.1c03541" target="_blank" >10.1021/acs.jpcb.1c03541</a>
Alternative languages
Result language
angličtina
Original language name
Recognition of N6-Methyladenosine by the YTHDC1 YTH Domain Studied by Molecular Dynamics and NMR Spectroscopy: The Role of Hydration
Original language description
The YTH domain of YTHDC1 belongs to a class of protein readers, recognizing the N6-methyladenosine (m(6)A) chemical modification in mRNA. Static ensemble-averaged structures revealed details of N6-methyl recognition via a conserved aromatic cage. Here, we performed molecular dynamics (MD) simulations along with nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC) to examine how dynamics and solvent interactions contribute to the m(6)A recognition and negative selectivity toward an unmethylated substrate. The structured water molecules surrounding the bound RNA and the methylated substrate's ability to exclude bulk water molecules contribute to the YTH domain's preference for m(6)A. Intrusions of bulk water deep into the binding pocket disrupt binding of unmethylated adenosine. The YTHDC1's preference for the 5'-Gm(6)A-3' motif is partially facilitated by a network of water-mediated interactions between the 2amino group of the guanosine and residues in the m(6)A binding pocket. The 5'-Im(6)A-3' (where I is inosine) motif can be recognized too, but disruption of the water network lowers affinity. The D479A mutant also disrupts the water network and destabilizes m(6)A binding. Our interdisciplinary study of the YTHDC1 protein-RNA complex reveals an unusual physical mechanism by which solvent interactions contribute toward m(6)A recognition.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10406 - Analytical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Physical Chemistry B
ISSN
1520-6106
e-ISSN
1520-5207
Volume of the periodical
125
Issue of the periodical within the volume
28
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
7691-7705
UT code for WoS article
000677581100012
EID of the result in the Scopus database
2-s2.0-85111217353