6U8V

Crystal structure of DNMT3B-DNMT3L in complex with CpGpT DNA

6U8V の概要

• エントリーDOI: 10.2210/pdb6u8v/pdb
• 分子名称: DNA (cytosine-5)-methyltransferase 3B, DNA (cytosine-5)-methyltransferase 3-like, CpGpT DNA (25-MER), ... (6 entities in total)
• 機能のキーワード: dnmt3b, dnmt3l, dna methylation, methyltransferase, transferase-dna complex, transferase, transferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 130915.61

構造登録者

Gao, L.,Zhang, Z.M.,Song, J. (登録日: 2019-09-06, 公開日: 2020-06-10, 最終更新日: 2024-12-25)

主引用文献

Gao, L.,Emperle, M.,Guo, Y.,Grimm, S.A.,Ren, W.,Adam, S.,Uryu, H.,Zhang, Z.M.,Chen, D.,Yin, J.,Dukatz, M.,Anteneh, H.,Jurkowska, R.Z.,Lu, J.,Wang, Y.,Bashtrykov, P.,Wade, P.A.,Wang, G.G.,Jeltsch, A.,Song, J.
Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms.
Nat Commun, 11:3355-3355, 2020

PubMed Abstract: Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterization of DNMT3A and DNMT3B, we here report a multi-layered substrate-recognition mechanism underpinning their divergent genomic methylation activities. A hydrogen bond in the catalytic loop of DNMT3B causes a lower CpG specificity than DNMT3A, while the interplay of target recognition domain and homodimeric interface fine-tunes the distinct target selection between the two enzymes, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. The divergent substrate preference between DNMT3A and DNMT3B provides an explanation for site-specific epigenomic alterations seen in ICF syndrome with DNMT3B mutations. Together, this study reveals distinctive substrate-readout mechanisms of the two DNMT3 enzymes, implicative of their differential roles during development and pathogenesis.

PubMed: 32620778
DOI: 10.1038/s41467-020-17109-4

実験手法

X-RAY DIFFRACTION (3 Å)