PDBsum entry 6rt4

RNA binding protein

PDB id: 6rt4

Contents

Protein chains

160 a.a.

DNA/RNA

Ligands

6MZ-_DC

SO4 ×6

Waters ×328

PDB id:

6rt4

Name:

RNA binding protein

Title:

The yth domain of ythdc1 protein in complex with m6acu oligonucleotide

Structure:

RNA (5'-r( (6Mz)p C)-3'). Chain: c, d. Engineered: yes. Yth domain-containing protein 1. Chain: b, a. Synonym: splicing factor yt521,yt521-b. Engineered: yes

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: ythdc1, kiaa1966, yt521. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.49Å R-factor: 0.205 R-free: 0.230

Authors:

R.Bedi,P.Sledz,A.Caflisch

Key ref:

Y.Li et al. (2019). Flexible Binding of m⁶A Reader Protein YTHDC1 to Its Preferred RNA Motif. J Chem Theory Comput, 15, 7004-7014. PubMed id: 31670957 DOI: 10.1021/acs.jctc.9b00987

Date:

22-May-19 Release date: 27-Nov-19

Protein chains

Q96MU7  (YTDC1_HUMAN) -  YTH domain-containing protein 1 from Homo sapiens

Seq: 727 a.a.

Struc: 160 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chain

6MZ-C-U 3 bases

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/acs.jctc.9b00987

J Chem Theory Comput 15:7004-7014 (2019)

PubMed id: 31670957

Flexible Binding of m⁶A Reader Protein YTHDC1 to Its Preferred RNA Motif.

Y.Li, R.K.Bedi, L.Wiedmer, D.Huang, P.Śledź, A.Caflisch.

ABSTRACT

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.