9szp

Crystal structure of the human YTHDC2 YTH domain in complex with m6A DNA

spinqualitylabelsall models 9szp, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9szp is a 2 chain structure with sequence from DNA molecule and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.58Å Ligands: 6MA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function YTDC2_HUMAN Publication Abstract from PubMed N6-methyladenosine (m(6)A) is the most prevalent internal modification in eukaryotic messenger RNA. Dysregulation of m(6)A-RNA signaling has been implicated in a wide range of human diseases. The N6-methyladenosine modifications in DNA (6mA) is much rarer, and its role is still debated. Here, we report the first holo crystal structure of the m(6)A-RNA reader YTHDC2. The 1.6 A resolution structure of YTHDC2 bound to the single-strand (ss) hexanucleotide GG(6mA)CTA-DNA shows an essentially identical binding mode of (6mA)CT-DNA as (m(6)A)CU-RNA in the other four human reader proteins YTHDC1 and YTHDF1-3. Comparative analysis of the binding of fluorescent-labeled 6mA-ssDNA and m(6)A-RNA revealed that the five human m(6)A-RNA readers exhibit slightly stronger binding affinity for 6mA-modified DNA with a factor ranging from about 1.3 for YTHDC1 to 30 for YTHDC2. Given the similar affinity and the similar binding mode of 6mA-ssDNA and m(6)A-RNA, we set up to develop a fluorescence polarization (FP) binding assay that uses a fluorescent-labeled 6mA-containing ssDNA as probe. The DNA-based FP assay shows high stability and robustness, making it suitable for high-throughput screening applications. The assay provides a powerful and cost-efficient platform to accelerate the discovery of small-molecule modulators targeting m(6)A-RNA reader proteins. A DNA-Based Binding Assay for the m(6)A-RNA Reader Proteins.,Bedi RK, Caflisch A Chembiochem. 2026 Mar 27;27(6):e202500897. doi: 10.1002/cbic.202500897. PMID:41863816 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA