3JBW

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

Summary for 3JBW

• Entry DOI: 10.2210/pdb3jbw/pdb
• Related: 3JBX 3JBY
• EMDB information: 6487 6488 6489 6490 6491
• Descriptor: V(D)J recombination-activating protein 1, V(D)J recombination-activating protein 2, 12-RSS signal end forward strand, ... (8 entities in total)
• Functional Keywords: rag1, rag2, v(d)j recombination, paired complex, antigen receptor gene recombination, t and b cell development, recombination-dna complex, recombination/dna
• Biological source: Danio rerio (zebra fish); More
• Total number of polymer chains: 10
• Total formula weight: 362687.86

Authors

Ru, H.,Chambers, M.G.,Fu, T.-M.,Tong, A.B.,Liao, M.,Wu, H. (deposition date: 2015-10-21, release date: 2015-12-09, Last modification date: 2024-02-21)

Primary citation

Ru, H.,Chambers, M.G.,Fu, T.M.,Tong, A.B.,Liao, M.,Wu, H.
Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures.
Cell(Cambridge,Mass.), 163:1138-1152, 2015

PubMed Abstract: 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 Å 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.

PubMed: 26548953
DOI: 10.1016/j.cell.2015.10.055

Experimental method

ELECTRON MICROSCOPY (4.6 Å)