3ASL

Structure of UHRF1 in complex with histone tail

Summary for 3ASL

• Entry DOI: 10.2210/pdb3asl/pdb
• Related: 2FAZ 2ZKD 2ZO0 3ASK 3CLZ 3DB3 3FL2
• Descriptor: E3 ubiquitin-protein ligase UHRF1, Histone H3.3, ZINC ION, ... (5 entities in total)
• Functional Keywords: histone reader module, epigenetic regulation, histone h3, ligase-dna binding protein complex, ligase/dna binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q96T88 P84243
• Total number of polymer chains: 2
• Total formula weight: 9682.32

Authors

Arita, K.,Sugita, K.,Unoki, M.,Hamamoto, R.,Sekiyama, N.,Tochio, H.,Ariyoshi, M.,Shirakawa, M. (deposition date: 2010-12-16, release date: 2012-01-25, Last modification date: 2024-03-13)

Primary citation

Arita, K.,Isogai, S.,Oda, T.,Unoki, M.,Sugita, K.,Sekiyama, N.,Kuwata, K.,Hamamoto, R.,Tochio, H.,Sato, M.,Ariyoshi, M.,Shirakawa, M.
Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1
Proc.Natl.Acad.Sci.USA, 109:12950-12955, 2012

PubMed Abstract: Multiple covalent modifications on a histone tail are often recognized by linked histone reader modules. UHRF1 [ubiquitin-like, containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1], an essential factor for maintenance of DNA methylation, contains linked two-histone reader modules, a tandem Tudor domain and a PHD finger, tethered by a 17-aa linker, and has been implicated to link histone modifications and DNA methylation. Here, we present the crystal structure of the linked histone reader modules of UHRF1 in complex with the amino-terminal tail of histone H3. Our structural and biochemical data provide the basis for combinatorial readout of unmodified Arg-2 (H3-R2) and methylated Lys-9 (H3-K9) by the tandem tudor domain and the PHD finger. The structure reveals that the intermodule linker plays an essential role in the formation of a histone H3-binding hole between the reader modules by making extended contacts with the tandem tudor domain. The histone H3 tail fits into the hole by adopting a compact fold harboring a central helix, which allows both of the reader modules to simultaneously recognize the modification states at H3-R2 and H3-K9. Our data also suggest that phosphorylation of a linker residue can modulate the relative position of the reader modules, thereby altering the histone H3-binding mode. This finding implies that the linker region plays a role as a functional switch of UHRF1 involved in multiple regulatory pathways such as maintenance of DNA methylation and transcriptional repression.

PubMed: 22837395
DOI: 10.1073/pnas.1203701109

Experimental method

X-RAY DIFFRACTION (1.41 Å)