1rmd: Difference between revisions

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<StructureSection load='1rmd' size='340' side='right' caption='[[1rmd]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='1rmd' size='340' side='right' caption='[[1rmd]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1rmd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RMD FirstGlance]. <br>
<table><tr><td colspan='2'>[[1rmd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RMD FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rmd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rmd RCSB], [http://www.ebi.ac.uk/pdbsum/1rmd PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rmd OCA], [http://pdbe.org/1rmd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rmd RCSB], [http://www.ebi.ac.uk/pdbsum/1rmd PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 1rmd" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Mus musculus]]
[[Category: Lk3 transgenic mice]]
[[Category: Bellon, S F]]
[[Category: Bellon, S F]]
[[Category: Coleman, J E]]
[[Category: Coleman, J E]]

Revision as of 13:17, 10 September 2015

RAG1 DIMERIZATION DOMAINRAG1 DIMERIZATION DOMAIN

Structural highlights

1rmd is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structure of the dimerization domain of the V(D)J recombination-activating protein, RAG1, was solved using zinc anomalous scattering. The structure reveals an unusual combination of multi-class zinc-binding motifs, including a zinc RING finger and a C2H2 zinc finger, that together from a single structural domain. The domain also contains a unique zinc binuclear cluster in place of a normally mononuclear zinc site in the RING finger. Together, four zinc ions help organize the entire domain, including the two helices that form the dimer interface.

Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster.,Bellon SF, Rodgers KK, Schatz DG, Coleman JE, Steitz TA Nat Struct Biol. 1997 Jul;4(7):586-91. PMID:9228952[14]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Schatz DG, Oettinger MA, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell. 1989 Dec 22;59(6):1035-48. PMID:2598259
  2. ↑ McBlane JF, van Gent DC, Ramsden DA, Romeo C, Cuomo CA, Gellert M, Oettinger MA. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell. 1995 Nov 3;83(3):387-95. PMID:8521468
  3. ↑ Agrawal A, Schatz DG. RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA containing signal ends in V(D)J recombination. Cell. 1997 Apr 4;89(1):43-53. PMID:9094713
  4. ↑ Landree MA, Wibbenmeyer JA, Roth DB. Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination. Genes Dev. 1999 Dec 1;13(23):3059-69. PMID:10601032
  5. ↑ Fugmann SD, Villey IJ, Ptaszek LM, Schatz DG. Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex. Mol Cell. 2000 Jan;5(1):97-107. PMID:10678172
  6. ↑ Yurchenko V, Xue Z, Sadofsky M. The RAG1 N-terminal domain is an E3 ubiquitin ligase. Genes Dev. 2003 Mar 1;17(5):581-5. PMID:12629039 doi:http://dx.doi.org/10.1101/gad.1058103
  7. ↑ Jones JM, Gellert M. Autoubiquitylation of the V(D)J recombinase protein RAG1. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15446-51. Epub 2003 Dec 11. PMID:14671314 doi:http://dx.doi.org/10.1073/pnas.2637012100
  8. ↑ Lu CP, Sandoval H, Brandt VL, Rice PA, Roth DB. Amino acid residues in Rag1 crucial for DNA hairpin formation. Nat Struct Mol Biol. 2006 Nov;13(11):1010-5. Epub 2006 Oct 8. PMID:17028591 doi:http://dx.doi.org/10.1038/nsmb1154
  9. ↑ Shimazaki N, Tsai AG, Lieber MR. H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning in trans in addition to tethering in cis: implications for translocations. Mol Cell. 2009 Jun 12;34(5):535-44. doi: 10.1016/j.molcel.2009.05.011. PMID:19524534 doi:http://dx.doi.org/10.1016/j.molcel.2009.05.011
  10. ↑ Simkus C, Makiya M, Jones JM. Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin ligase. Mol Immunol. 2009 Apr;46(7):1319-25. doi: 10.1016/j.molimm.2008.11.009. Epub 2008, Dec 31. PMID:19118899 doi:http://dx.doi.org/10.1016/j.molimm.2008.11.009
  11. ↑ Hewitt SL, Yin B, Ji Y, Chaumeil J, Marszalek K, Tenthorey J, Salvagiotto G, Steinel N, Ramsey LB, Ghysdael J, Farrar MA, Sleckman BP, Schatz DG, Busslinger M, Bassing CH, Skok JA. RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol. 2009 Jun;10(6):655-64. doi: 10.1038/ni.1735. PMID:19448632 doi:http://dx.doi.org/10.1038/ni.1735
  12. ↑ Grazini U, Zanardi F, Citterio E, Casola S, Goding CR, McBlane F. The RING domain of RAG1 ubiquitylates histone H3: a novel activity in chromatin-mediated regulation of V(D)J joining. Mol Cell. 2010 Jan 29;37(2):282-93. doi: 10.1016/j.molcel.2009.12.035. PMID:20122409 doi:http://dx.doi.org/10.1016/j.molcel.2009.12.035
  13. ↑ Yin FF, Bailey S, Innis CA, Ciubotaru M, Kamtekar S, Steitz TA, Schatz DG. Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis. Nat Struct Mol Biol. 2009 May;16(5):499-508. Epub 2009 Apr 26. PMID:19396172 doi:http://dx.doi.org/10.1038/nsmb.1593
  14. ↑ Bellon SF, Rodgers KK, Schatz DG, Coleman JE, Steitz TA. Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster. Nat Struct Biol. 1997 Jul;4(7):586-91. PMID:9228952

1rmd, resolution 2.10Å

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