2v88

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{{STRUCTURE_2v88| PDB=2v88 | SCENE= }}
{{STRUCTURE_2v88| PDB=2v88 | SCENE= }}
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'''CRYSTAL STRUCTURE OF RAG2-PHD FINGER IN COMPLEX WITH H3R2ME2SK4ME2 PEPTIDE'''
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===CRYSTAL STRUCTURE OF RAG2-PHD FINGER IN COMPLEX WITH H3R2ME2SK4ME2 PEPTIDE===
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==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Recombinase]]
[[Category: Recombinase]]
[[Category: Symmetric dimethylated arginine]]
[[Category: Symmetric dimethylated arginine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:05:44 2008''

Revision as of 13:05, 27 July 2008

Template:STRUCTURE 2v88

CRYSTAL STRUCTURE OF RAG2-PHD FINGER IN COMPLEX WITH H3R2ME2SK4ME2 PEPTIDE

Template:ABSTRACT PUBMED 18025461

About this Structure

2V88 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

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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