6UCA

Crystal structure of human ZCCHC4 in complex with SAH

Summary for 6UCA

• Entry DOI: 10.2210/pdb6uca/pdb
• Descriptor: rRNA N6-adenosine-methyltransferase ZCCHC4, S-ADENOSYL-L-HOMOCYSTEINE, ZINC ION (3 entities in total)
• Functional Keywords: 28s rna m6a methyltransferase, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 309547.25

Authors

Lu, J.W.,Ren, W.D.,Huang, M.J.,Gao, L.,Li, D.X.,Wang, G.G.,Song, J. (deposition date: 2019-09-15, release date: 2019-10-16, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.103 Å)