6b40: Difference between revisions

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<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=6b40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b40 OCA], [http://pdbe.org/6b40 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b40 RCSB], [http://www.ebi.ac.uk/pdbsum/6b40 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b40 ProSAT]</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=6b40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b40 OCA], [http://pdbe.org/6b40 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b40 RCSB], [http://www.ebi.ac.uk/pdbsum/6b40 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b40 ProSAT]</span></td></tr>
</table>
</table>
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== Publication Abstract from PubMed ==
Domestication of a transposon (a DNA sequence that can change its position in a genome) to give rise to the RAG1-RAG2 recombinase (RAG) and V(D)J recombination, which produces the diverse repertoire of antibodies and T cell receptors, was a pivotal event in the evolution of the adaptive immune system of jawed vertebrates. The evolutionary adaptations that transformed the ancestral RAG transposase into a RAG recombinase with appropriately regulated DNA cleavage and transposition activities are not understood. Here, beginning with cryo-electron microscopy structures of the amphioxus ProtoRAG transposase (an evolutionary relative of RAG), we identify amino acid residues and domains the acquisition or loss of which underpins the propensity of RAG for coupled cleavage, its preference for asymmetric DNA substrates and its inability to perform transposition in cells. In particular, we identify two adaptations specific to jawed-vertebrates-arginine 848 in RAG1 and an acidic region in RAG2-that together suppress RAG-mediated transposition more than 1,000-fold. Our findings reveal a two-tiered mechanism for the suppression of RAG-mediated transposition, illuminate the evolution of V(D)J recombination and provide insight into the principles that govern the molecular domestication of transposons.
Transposon molecular domestication and the evolution of the RAG recombinase.,Zhang Y, Cheng TC, Huang G, Lu Q, Surleac MD, Mandell JD, Pontarotti P, Petrescu AJ, Xu A, Xiong Y, Schatz DG Nature. 2019 Apr 10. pii: 10.1038/s41586-019-1093-7. doi:, 10.1038/s41586-019-1093-7. PMID:30971819<ref>PMID:30971819</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6b40" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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Revision as of 10:46, 24 April 2019

BbRAGL-3'TIR synaptic complex with nicked DNA refined with C2 symmetryBbRAGL-3'TIR synaptic complex with nicked DNA refined with C2 symmetry

Structural highlights

6b40 is a 10 chain structure with sequence from Amphioxus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
NonStd Res:
Gene:RAG1L (Amphioxus), RAG2L (Amphioxus)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Domestication of a transposon (a DNA sequence that can change its position in a genome) to give rise to the RAG1-RAG2 recombinase (RAG) and V(D)J recombination, which produces the diverse repertoire of antibodies and T cell receptors, was a pivotal event in the evolution of the adaptive immune system of jawed vertebrates. The evolutionary adaptations that transformed the ancestral RAG transposase into a RAG recombinase with appropriately regulated DNA cleavage and transposition activities are not understood. Here, beginning with cryo-electron microscopy structures of the amphioxus ProtoRAG transposase (an evolutionary relative of RAG), we identify amino acid residues and domains the acquisition or loss of which underpins the propensity of RAG for coupled cleavage, its preference for asymmetric DNA substrates and its inability to perform transposition in cells. In particular, we identify two adaptations specific to jawed-vertebrates-arginine 848 in RAG1 and an acidic region in RAG2-that together suppress RAG-mediated transposition more than 1,000-fold. Our findings reveal a two-tiered mechanism for the suppression of RAG-mediated transposition, illuminate the evolution of V(D)J recombination and provide insight into the principles that govern the molecular domestication of transposons.

Transposon molecular domestication and the evolution of the RAG recombinase.,Zhang Y, Cheng TC, Huang G, Lu Q, Surleac MD, Mandell JD, Pontarotti P, Petrescu AJ, Xu A, Xiong Y, Schatz DG Nature. 2019 Apr 10. pii: 10.1038/s41586-019-1093-7. doi:, 10.1038/s41586-019-1093-7. PMID:30971819[1]

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

References

  1. Zhang Y, Cheng TC, Huang G, Lu Q, Surleac MD, Mandell JD, Pontarotti P, Petrescu AJ, Xu A, Xiong Y, Schatz DG. Transposon molecular domestication and the evolution of the RAG recombinase. Nature. 2019 Apr 10. pii: 10.1038/s41586-019-1093-7. doi:, 10.1038/s41586-019-1093-7. PMID:30971819 doi:http://dx.doi.org/10.1038/s41586-019-1093-7

6b40, resolution 4.30Å

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