7V0E

Crystal structure of the macro-oligomeric form of DNMT3B methyltransferase domain.

7V0E の概要

• エントリーDOI: 10.2210/pdb7v0e/pdb
• 分子名称: DNA (cytosine-5)-methyltransferase 3B, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• 機能のキーワード: dnmt3b, dna methylation, methyltransferase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 263328.29

構造登録者

Gao, L.,Lu, J.,Song, J. (登録日: 2022-05-10, 公開日: 2022-06-22, 最終更新日: 2023-10-18)

主引用文献

Gao, L.,Guo, Y.,Biswal, M.,Lu, J.,Yin, J.,Fang, J.,Chen, X.,Shao, Z.,Huang, M.,Wang, Y.,Wang, G.G.,Song, J.
Structure of DNMT3B homo-oligomer reveals vulnerability to impairment by ICF mutations.
Nat Commun, 13:4249-4249, 2022

PubMed Abstract: DNA methyltransferase DNMT3B plays an essential role in establishment of DNA methylation during embryogenesis. Mutations of DNMT3B are associated with human diseases, notably the immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome. How ICF mutations affect DNMT3B activity is not fully understood. Here we report the homo-oligomeric structure of DNMT3B methyltransferase domain, providing insight into DNMT3B-mediated DNA methylation in embryonic stem cells where the functional regulator DNMT3L is dispensable. The interplay between one of the oligomer interfaces (FF interface) and the catalytic loop renders DNMT3B homo-oligomer a conformation and activity distinct from the DNMT3B-DNMT3L heterotetramer, and a greater vulnerability to certain ICF mutations. Biochemical and cellular analyses further reveal that the ICF mutations of FF interface impair the DNA binding and heterochromatin targeting of DNMT3B, leading to reduced DNA methylation in cells. Together, this study provides a mechanistic understanding of DNMT3B-mediated DNA methylation and its dysregulation in disease.

PubMed: 35869095
DOI: 10.1038/s41467-022-31933-w

実験手法

X-RAY DIFFRACTION (3.27016388184 Å)