6B92

Crystal Structure of the N-terminal domain of human METTL16 in complex with SAH

Summary for 6B92

• Entry DOI: 10.2210/pdb6b92/pdb
• Related: 6B91
• Descriptor: U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase, 1,2-ETHANEDIOL, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: methyltransferase-like protein 16, rna methylation, n6-methyladenosine, s-adenosylmethionine, s-adenosylhomocysteine, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 34250.48

Authors

Ruszkowska, A.,Ruszkowski, M.,Dauter, Z.,Brown, J.A. (deposition date: 2017-10-09, release date: 2018-04-04, Last modification date: 2023-10-04)

Primary citation

Ruszkowska, A.,Ruszkowski, M.,Dauter, Z.,Brown, J.A.
Structural insights into the RNA methyltransferase domain of METTL16.
Sci Rep, 8:5311-5311, 2018

PubMed Abstract: N-methyladenosine (mA) is an abundant modification in messenger RNA and noncoding RNAs that affects RNA metabolism. Methyltransferase-like protein 16 (METTL16) is a recently confirmed mA RNA methyltransferase that methylates U6 spliceosomal RNA and interacts with the 3'-terminal RNA triple helix of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). Here, we present two X-ray crystal structures of the N-terminal methyltransferase domain (residues 1-291) of human METTL16 (METTL16_291): an apo structure at 1.9 Å resolution and a post-catalytic S-adenosylhomocysteine-bound complex at 2.1 Å resolution. The structures revealed a highly conserved Rossmann fold that is characteristic of Class I S-adenosylmethionine-dependent methyltransferases and a large, positively charged groove. This groove likely represents the RNA-binding site and it includes structural elements unique to METTL16. In-depth analysis of the active site led to a model of the methyl transfer reaction catalyzed by METTL16. In contrast to the major mA methyltransferase heterodimer METTL3/METTL14, full-length METTL16 forms a homodimer and METTL16_291 exists as a monomer based on size-exclusion chromatography. A native gel-shift assay shows that METTL16 binds to the MALAT1 RNA triple helix, but monomeric METTL16_291 does not. Our results provide insights into the molecular structure of METTL16, which is distinct from METTL3/METTL14.

PubMed: 29593291
DOI: 10.1038/s41598-018-23608-8

Experimental method

X-RAY DIFFRACTION (2.1 Å)