Recognition of asymmetrically dimethylated arginine by TDRD3.
Asymmetric dimethylarginine (aDMA) marks are placed on histones and the C-terminal domain (CTD) of RNA Polymerase II (RNAP II) and serve as a signal for recruitment of appropriate transcription and processing factors in coordination with transcription cycle. In contrast to other Tudor domain-containing proteins, Tudor domain-containing protein 3 (TDRD3) associates selectively with the aDMA marks but not with other methylarginine motifs. Here, we report the solution structure of the Tudor domain of TDRD3 bound to the asymmetrically dimethylated CTD. The structure and mutational analysis provide a molecular basis for how TDRD3 recognizes the aDMA mark. The unique aromatic cavity of the TDRD3 Tudor domain with a tyrosine in position 566 creates a selectivity filter for the aDMA residue. Our work contributes to the understanding of substrate selectivity rules of the Tudor aromatic cavity, which is an important structural motif for reading of methylation marks.
CEITEC-Central European Institute of Technology, Masaryk University, CZ-62500 Brno, Czech Republic.
Tomas
T
Sikorsky
Fruzsina
F
Hobor
Eva
E
Krizanova
Josef
J
Pasulka
Karel
K
Kubicek
Richard
R
Stefl
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment
D000596:Amino Acids; D011506:Proteins; C532746:Tdrd3 protein, human; C018524:N,N-dimethylarginine; D001120:Arginine