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3jbw

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Revision as of 17:39, 6 March 2020

Cryo-electron microscopy structure of RAG Paired Complex (with NBD, no symmetry)

3jbw, resolution 4.63Å

Structural highlights

3jbw is a 10 chain structure with sequence from Brachidanio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3jbx, 3jby
Gene:	rag1 (Brachidanio rerio), rag2, rag-2 (Brachidanio rerio)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RAG1_DANRE] 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. 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 (By similarity).

Publication Abstract from PubMed

Diverse repertoires of antigen-receptor genes that result from combinatorial splicing of coding segments by V(D)J recombination are hallmarks of vertebrate immunity. The (RAG1-RAG2)2 recombinase (RAG) recognizes recombination signal sequences (RSSs) containing a heptamer, a spacer of 12 or 23 base pairs, and a nonamer (12-RSS or 23-RSS) and introduces precise breaks at RSS-coding segment junctions. RAG forms synaptic complexes only with one 12-RSS and one 23-RSS, a dogma known as the 12/23 rule that governs the recombination fidelity. We report cryo-electron microscopy structures of synaptic RAG complexes at up to 3.4 A resolution, which reveal a closed conformation with base flipping and base-specific recognition of RSSs. Distortion at RSS-coding segment junctions and base flipping in coding segments uncover the two-metal-ion catalytic mechanism. Induced asymmetry involving tilting of the nonamer-binding domain dimer of RAG1 upon binding of HMGB1-bent 12-RSS or 23-RSS underlies the molecular mechanism for the 12/23 rule.

Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures.,Ru H, Chambers MG, Fu TM, Tong AB, Liao M, Wu H Cell. 2015 Nov 19;163(5):1138-52. doi: 10.1016/j.cell.2015.10.055. Epub 2015 Nov , 5. PMID:26548953^[1]

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

References

↑ Ru H, Chambers MG, Fu TM, Tong AB, Liao M, Wu H. Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures. Cell. 2015 Nov 19;163(5):1138-52. doi: 10.1016/j.cell.2015.10.055. Epub 2015 Nov , 5. PMID:26548953 doi:http://dx.doi.org/10.1016/j.cell.2015.10.055

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3jbw"

@@ Line 1: / Line 1: @@
 ==Cryo-electron microscopy structure of RAG Paired Complex (with NBD, no symmetry)==
-<StructureSection load='3jbw' size='340' side='right' caption='[[3jbw]], [[Resolution|resolution]] 4.63&Aring;' scene=''>
+<SX load='3jbw' size='340' side='right' viewer='molstar' caption='[[3jbw]], [[Resolution|resolution]] 4.63&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3jbw]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JBW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBW FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 3jbw" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Recombination-activating gene|Recombination-activating gene]]
+*[[Recombination-activating gene 3D structures|Recombination-activating gene 3D structures]]
 == References ==
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Brachidanio rerio]]
+[[Category: Large Structures]]
 [[Category: Chambers, M G]]
 [[Category: Fu, T M]]

3jbw

From Proteopedia

Revision as of 17:39, 6 March 2020

Cryo-electron microscopy structure of RAG Paired Complex (with NBD, no symmetry)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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