2v85
CRYSTAL STRUCTURE OF RAG2-PHD FINGER IN COMPLEX WITH H3R2ME1K4ME3 PEPTIDE
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OverviewOverview
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.
About this StructureAbout this Structure
2V85 is a Single protein structure of sequence from Mus musculus with as ligand. Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.
ReferenceReference
The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2., Ramon-Maiques S, Kuo AJ, Carney D, Matthews AG, Oettinger MA, Gozani O, Yang W, Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):18993-8. Epub 2007 Nov 19. PMID:18025461
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