Crystal structures of the Tudor domains of human PHF20 reveal novel structural variations on the Royal Family of proteins

The human PHD finger protein 20 (PHF20) is a putative transcription factor. While little is known about its cognate cellular role, antibodies against PHF20 are present in sera from patients with hepatocellular carcinoma, glioblastoma and childhood medulloblastula. PHF20 comprises two N-terminal Tudor domains, a central C2H2-link zinc finger domain and a C-terminal zinc-binding PHD domain, and is a component of some MLL methyltransferase complexes. Here, we report the crystal structures of the N-terminal Tudor domains of PHF20 and highlight the novel structural features of each domain. We also confirm previous studies suggesting that the second Tudor domain of PHF20 exhibits preference for dimethylated histone substrates.

► Crystal structures of both Tudor domains of PHF20 are presented individually.
► The first Tudor domain contains an occluded aromatic cage.
► The first Tudor domain may be a proline motif binding domain.
► The second Tudor domain is shown to preferentially bind dimethylated histones.