2V89

Crystal structure of RAG2-PHD finger in complex with H3K4me3 peptide at 1.1A resolution

Summary for 2V89

• Entry DOI: 10.2210/pdb2v89/pdb
• Related: 2A23 2V83 2V85 2V86 2V87 2V88
• Descriptor: VDJ RECOMBINATION-ACTIVATING PROTEIN 2, HISTONE H3, ZINC ION, ... (4 entities in total)
• Functional Keywords: v(d)j recombination, covalent modifications, rag, histone, nucleus, nuclease, hydrolase, phd finger, dna-binding, recombinase, endonuclease, trimethyl lysine, dna recombination, protein binding
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Total number of polymer chains: 4
• Total formula weight: 21163.22

Authors

Ramon-Maiques, S.,Yang, W. (deposition date: 2007-08-03, release date: 2007-12-11, Last modification date: 2023-12-13)

Primary citation

Matthews, A.G.W.,Kuo, A.J.,Ramon-Maiques, S.,Han, S.,Champagne, K.S.,Ivanov, D.,Gallardo, M.,Carney, D.,Cheung, P.,Ciccone, D.N.,Walter, K.L.,Utz, P.J.,Shi, Y.,Kutateladze, T.G.,Yang, W.,Gozani, O.,Oettinger, M.A.
Rag2 Phd Finger Couples Histone H3 Lysine 4 Trimethylation with V(D)J Recombination.
Nature, 450:1106-, 2007

PubMed Abstract: Nuclear processes such as transcription, DNA replication and recombination are dynamically regulated by chromatin structure. Eukaryotic transcription is known to be regulated by chromatin-associated proteins containing conserved protein domains that specifically recognize distinct covalent post-translational modifications on histones. However, it has been unclear whether similar mechanisms are involved in mammalian DNA recombination. Here we show that RAG2--an essential component of the RAG1/2 V(D)J recombinase, which mediates antigen-receptor gene assembly--contains a plant homeodomain (PHD) finger that specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3). The high-resolution crystal structure of the mouse RAG2 PHD finger bound to H3K4me3 reveals the molecular basis of H3K4me3-recognition by RAG2. Mutations that abrogate RAG2's recognition of H3K4me3 severely impair V(D)J recombination in vivo. Reducing the level of H3K4me3 similarly leads to a decrease in V(D)J recombination in vivo. Notably, a conserved tryptophan residue (W453) that constitutes a key structural component of the K4me3-binding surface and is essential for RAG2's recognition of H3K4me3 is mutated in patients with immunodeficiency syndromes. Together, our results identify a new function for histone methylation in mammalian DNA recombination. Furthermore, our results provide the first evidence indicating that disrupting the read-out of histone modifications can cause an inherited human disease.

PubMed: 18033247
DOI: 10.1038/NATURE06431

Experimental method

X-RAY DIFFRACTION (1.1 Å)