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PDBsum entry 6rt5
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RNA binding protein
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PDB id
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6rt5
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References listed in PDB file
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Key reference
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Title
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Flexible binding of m6a reader protein ythdc1 to its preferred RNA motif.
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Authors
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Y.Li,
R.K.Bedi,
L.Wiedmer,
D.Huang,
P.ŚLedź,
A.Caflisch.
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Ref.
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J Chem Theory Comput, 2019,
15,
7004-7014.
[DOI no: ]
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PubMed id
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Abstract
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N6-Methyladenosine (m6A) is the most prevalent
chemical modification in human mRNAs. Its recognition by reader proteins enables
many cellular functions, including splicing and translation of mRNAs. However,
the binding mechanisms of m6A-containing RNAs to their readers are
still elusive due to the unclear roles of m6A-flanking
ribonucleotides. Here, we use a model system, YTHDC1 with its RNA motif
5'-G-2G-1(m6A)C+1U+2-3',
to investigate the binding mechanisms by atomistic simulations, X-ray
crystallography, and isothermal titration calorimetry. The experimental data and
simulation results show that m6A is captured by an aromatic cage of
YTHDC1 and the 3' terminus nucleotides are stabilized by cation-π-π
interactions, while the 5' terminus remains flexible. Notably, simulations of
unbound RNA motifs reveal that the methyl group of m6A and the 5'
terminus shift the conformational preferences of the oligoribonucleotide to the
bound-like conformation, thereby facilitating the association process. The
binding mechanisms may help in the discovery of chemical probes against
m6A reader proteins.
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