3ZPV

Crystal structure of Drosophila Pygo PHD finger in complex with Legless HD1 domain

Summary for 3ZPV

• Entry DOI: 10.2210/pdb3zpv/pdb
• Descriptor: PROTEIN BCL9 HOMOLOG, PROTEIN PYGOPUS, ZINC ION, ... (5 entities in total)
• Functional Keywords: transcription, wnt signaling pathway, zn finger, histone h3 tail binding
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY); More
• Cellular location: Nucleus: Q961D9 Q9V9W8 Q9V9W8
• Total number of polymer chains: 36
• Total formula weight: 199415.08

Authors

Miller, T.C.R.,Mieszczanek, J.,Sanchez-Barrena, M.J.,Rutherford, T.J.,Fiedler, M.,Bienz, M. (deposition date: 2013-03-02, release date: 2013-10-30, Last modification date: 2023-12-20)

Primary citation

Miller, T.C.R.,Mieszczanek, J.,Sanchez-Barrena, M.J.,Rutherford, T.J.,Fiedler, M.,Bienz, M.
Evolutionary Adaptation of the Fly Pygo Phd Finger Towards Recognizing Histone H3 Tail Methylated at Arginine 2
Structure, 21:2208-, 2013

PubMed Abstract: Pygo proteins promote Armadillo- and β-catenin-dependent transcription, by relieving Groucho-dependent repression of Wnt targets. Their PHD fingers bind histone H3 tail methylated at lysine 4, and to the HD1 domain of their Legless/BCL9 cofactors, linking Pygo to Armadillo/β-catenin. Intriguingly, fly Pygo orthologs exhibit a tryptophan > phenylalanine substitution in their histone pocket-divider which reduces their affinity for histones. Here, we use X-ray crystallography and NMR, to discover a conspicuous groove bordering this phenylalanine in the Drosophila PHD-HD1 complex--a semi-aromatic cage recognizing asymmetrically methylated arginine 2 (R2me2a), a chromatin mark of silenced genes. Our structural model of the ternary complex reveals a distinct mode of dimethylarginine recognition, involving a polar interaction between R2me2a and its groove, the structural integrity of which is crucial for normal tissue patterning. Notably, humanized fly Pygo derepresses Notch targets, implying an inherent Notch-related function of classical Pygo orthologs, disabled in fly Pygo, which thus appears dedicated to Wnt signaling.

PubMed: 24183574
DOI: 10.1016/J.STR.2013.09.013

Experimental method

X-RAY DIFFRACTION (2.68 Å)