6UCA

Crystal structure of human ZCCHC4 in complex with SAH

6UCA の概要

• エントリーDOI: 10.2210/pdb6uca/pdb
• 分子名称: rRNA N6-adenosine-methyltransferase ZCCHC4, S-ADENOSYL-L-HOMOCYSTEINE, ZINC ION (3 entities in total)
• 機能のキーワード: 28s rna m6a methyltransferase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 309547.25

構造登録者

Lu, J.W.,Ren, W.D.,Huang, M.J.,Gao, L.,Li, D.X.,Wang, G.G.,Song, J. (登録日: 2019-09-15, 公開日: 2019-10-16, 最終更新日: 2024-03-13)

主引用文献

Ren, W.,Lu, J.,Huang, M.,Gao, L.,Li, D.,Wang, G.G.,Song, J.
Structure and regulation of ZCCHC4 in m6A-methylation of 28S rRNA.
Nat Commun, 10:5042-5042, 2019

PubMed Abstract: N-methyladenosine (mA) modification provides an important epitranscriptomic mechanism that critically regulates RNA metabolism and function. However, how mA writers attain substrate specificities remains unclear. We report the 3.1 Å-resolution crystal structure of human CCHC zinc finger-containing protein ZCCHC4, a 28S rRNA-specific mA methyltransferase, bound to S-adenosyl-L-homocysteine. The methyltransferase (MTase) domain of ZCCHC4 is packed against N-terminal GRF-type and C2H2 zinc finger domains and a C-terminal CCHC domain, creating an integrated RNA-binding surface. Strikingly, the MTase domain adopts an autoinhibitory conformation, with a self-occluded catalytic site and a fully-closed cofactor pocket. Mutational and enzymatic analyses further substantiate the molecular basis for ZCCHC4-RNA recognition and a role of the stem-loop structure within substrate in governing the substrate specificity. Overall, this study unveils unique structural and enzymatic characteristics of ZCCHC4, distinctive from what was seen with the METTL family of mA writers, providing the mechanistic basis for ZCCHC4 modulation of mA RNA methylation.

PubMed: 31695039
DOI: 10.1038/s41467-019-12923-x

実験手法

X-RAY DIFFRACTION (3.103 Å)