2VPG

Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex

Summary for 2VPG

• Entry DOI: 10.2210/pdb2vpg/pdb
• Related: 2VP7 2VPB 2VPD 2VPE
• Descriptor: PYGOPUS HOMOLOG 1, B-CELL CLL/LYMPHOMA 9 PROTEIN, HISTONE H3 TAIL, ... (6 entities in total)
• Functional Keywords: gene regulation, wnt signaling pathway, wnt signaling complex, chromosomal rearrangement, signaling protein, bcl9 hd1 domain, hpygo1 phd domain, proto-oncogene, phosphoprotein, histone h3k4me2, zinc, nucleus, zinc-finger, metal-binding
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 6
• Total formula weight: 24769.69

Authors

Fiedler, M.,Sanchez-Barrena, M.J.,Nekrasov, M.,Mieszczanek, J.,Rybin, V.,Muller, J.,Bienz, M.,Evans, P. (deposition date: 2008-02-27, release date: 2008-06-17, Last modification date: 2023-12-13)

Primary citation

Fiedler, M.,Sanchez-Barrena, M.J.,Nekrasov, M.,Mieszczanek, J.,Rybin, V.,Muller, J.,Evans, P.,Bienz, M.
Decoding of Methylated Histone H3 Tail by the Pygo- Bcl9 Wnt Signaling Complex.
Mol.Cell, 30:507-, 2008

PubMed Abstract: Pygo and BCL9/Legless transduce the Wnt signal by promoting the transcriptional activity of beta-catenin/Armadillo in normal and malignant cells. We show that human and Drosophila Pygo PHD fingers associate with their cognate HD1 domains from BCL9/Legless to bind specifically to the histone H3 tail methylated at lysine 4 (H3K4me). The crystal structures of ternary complexes between PHD, HD1, and two different H3K4me peptides reveal a unique mode of histone tail recognition: efficient histone binding requires HD1 association, and the PHD-HD1 complex binds preferentially to H3K4me2 while displaying insensitivity to methylation of H3R2. Therefore, this is a prime example of histone tail binding by a PHD finger (of Pygo) being modulated by a cofactor (BCL9/Legless). Rescue experiments in Drosophila indicate that Wnt signaling outputs depend on histone decoding. The specificity of this process provided by the Pygo-BCL9/Legless complex suggests that this complex facilitates an early step in the transition from gene silence to Wnt-induced transcription.

PubMed: 18498752
DOI: 10.1016/J.MOLCEL.2008.03.011

Experimental method

X-RAY DIFFRACTION (1.6 Å)