The Molecular Basis of Human ALKBH3 Mediated RNA N¹ -methyladenosine (m¹ A) Demethylation.

ABSTRACT: N¹ -methyladenosine (m¹ A) is a prevalent post-transcriptional RNA modification, and the distribution and dynamics of the modification play key epitranscriptomic roles in cell development. At present, the human AlkB Fe(II)/α-ketoglutarate-dependent dioxygenase family member ALKBH3 is the only known mRNA m¹ A demethylase, but its catalytic mechanism remains unclear. Here, we present the structures of ALKBH3-oligo crosslinked complexes obtained with the assistance of a synthetic antibody crystallization chaperone. Structural and biochemical results showed that ALKBH3 utilized two β-hairpins (β4-loop-β5 and β'-loop-β'') and the α2 helix to facilitate single-stranded substrate binding. Moreover, a bubble-like region around Asp194 and a key residue inside the ac

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11846542 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature