View source for 3gnb


==Crystal structure of the RAG1 nonamer-binding domain with DNA==
<StructureSection load='3gnb' size='340' side='right'caption='[[3gnb]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gnb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GNB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnb OCA], [https://pdbe.org/3gnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gnb RCSB], [https://www.ebi.ac.uk/pdbsum/3gnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gnb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RAG1_MOUSE RAG1_MOUSE] Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.<ref>PMID:2598259</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:10601032</ref> <ref>PMID:10678172</ref> <ref>PMID:12629039</ref> <ref>PMID:14671314</ref> <ref>PMID:17028591</ref> <ref>PMID:19524534</ref> <ref>PMID:19118899</ref> <ref>PMID:19448632</ref> <ref>PMID:20122409</ref> <ref>PMID:19396172</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gn/3gnb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gnb ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
The products of recombination-activating genes RAG1 and RAG2 mediate the assembly of antigen receptor genes during lymphocyte development in a process known as V(D)J recombination. Lack of structural information for the RAG proteins has hindered mechanistic studies of this reaction. We report here the crystal structure of an essential DNA binding domain of the RAG1 catalytic core bound to its nonamer DNA recognition motif. The RAG1 nonamer binding domain (NBD) forms a tightly interwoven dimer that binds and synapses two nonamer elements, with each NBD making contact with both DNA molecules. Biochemical and biophysical experiments confirm that the two nonamers are in close proximity in the RAG1/2-DNA synaptic complex and demonstrate the functional importance of the protein-DNA contacts revealed in the structure. These findings reveal a previously unsuspected function for the NBD in DNA synapsis and have implications for the regulation of DNA binding and cleavage by RAG1 and RAG2.

Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis.,Yin FF, Bailey S, Innis CA, Ciubotaru M, Kamtekar S, Steitz TA, Schatz DG Nat Struct Mol Biol. 2009 May;16(5):499-508. Epub 2009 Apr 26. PMID:19396172<ref>PMID:19396172</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3gnb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Recombination-activating gene 3D structures|Recombination-activating gene 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Bailey S]]
[[Category: Innis CA]]
[[Category: Schatz DG]]
[[Category: Steitz TA]]
[[Category: Yin FF]]