2V87

Crystal structure of RAG2-PHD finger in complex with H3R2me2sK4me3 peptide

Summary for 2V87

• Entry DOI: 10.2210/pdb2v87/pdb
• Related: 2A23 2V83 2V85 2V86 2V88 2V89
• Descriptor: VDJ RECOMBINATION-ACTIVATING PROTEIN 2, HISTONE H3.2, 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, symmetric dimethylated arginine, protein binding, trimethyl lysine, dna recombination
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Total number of polymer chains: 4
• Total formula weight: 21851.96

Authors

Ramon-Maiques, S.,Yang, W. (deposition date: 2007-08-02, release date: 2007-12-11, Last modification date: 2023-12-13)

Primary citation

Ramon-Maiques, S.,Kuo, A.J.,Carney, D.,Matthews, A.G.W.,Oettinger, M.A.,Gozani, O.,Yang, W.
The Plant Homeodomain Finger of Rag2 Recognizes Histone H3 Methylated at Both Lysine-4 and Arginine-2.
Proc.Natl.Acad.Sci.USA, 104:18993-, 2007

PubMed Abstract: Recombination activating gene (RAG) 1 and RAG2 together catalyze V(D)J gene rearrangement in lymphocytes as the first step in the assembly and maturation of antigen receptors. RAG2 contains a plant homeodomain (PHD) near its C terminus (RAG2-PHD) that recognizes histone H3 methylated at lysine 4 (H3K4me) and influences V(D)J recombination. We report here crystal structures of RAG2-PHD alone and complexed with five modified H3 peptides. Two aspects of RAG2-PHD are unique. First, in the absence of the modified peptide, a peptide N-terminal to RAG2-PHD occupies the substrate-binding site, which may reflect an autoregulatory mechanism. Second, in contrast to other H3K4me3-binding PHD domains, RAG2-PHD substitutes a carboxylate that interacts with arginine 2 (R2) with a Tyr, resulting in binding to H3K4me3 that is enhanced rather than inhibited by dimethylation of R2. Five residues involved in histone H3 recognition were found mutated in severe combined immunodeficiency (SCID) patients. Disruption of the RAG2-PHD structure appears to lead to the absence of T and B lymphocytes, whereas failure to bind H3K4me3 is linked to Omenn Syndrome. This work provides a molecular basis for chromatin-dependent gene recombination and presents a single protein domain that simultaneously recognizes two distinct histone modifications, revealing added complexity in the read-out of combinatorial histone modifications.

PubMed: 18025461
DOI: 10.1073/PNAS.0709170104

Experimental method

X-RAY DIFFRACTION (1.8 Å)