6CG0

Cryo-EM structure of mouse RAG1/2 HFC complex (3.17 A)

6CG0 の概要

• エントリーDOI: 10.2210/pdb6cg0/pdb
• EMDBエントリー: 7470
• 分子名称: V(D)J recombination-activating protein 1, ZINC ION, CALCIUM ION, ... (11 entities in total)
• 機能のキーワード: v(d)j recombination, rag1/2, rss, immunity, recombination
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 373404.49

構造登録者

Chen, X.,Kim, M.,Chuenchor, W.,Cui, Y.,Zhang, X.,Zhou, Z.H.,Gellert, M.,Yang, W. (登録日: 2018-02-19, 公開日: 2018-04-25, 最終更新日: 2025-05-14)

主引用文献

Kim, M.S.,Chuenchor, W.,Chen, X.,Cui, Y.,Zhang, X.,Zhou, Z.H.,Gellert, M.,Yang, W.
Cracking the DNA Code for V(D)J Recombination.
Mol. Cell, 70:358-370.e4, 2018

PubMed Abstract: To initiate V(D)J recombination for generating the adaptive immune response of vertebrates, RAG1/2 recombinase cleaves DNA at a pair of recombination signal sequences, the 12- and 23-RSS. We have determined crystal and cryo-EM structures of RAG1/2 with DNA in the pre-reaction and hairpin-forming complexes up to 2.75 Å resolution. Both protein and DNA exhibit structural plasticity and undergo dramatic conformational changes. Coding-flank DNAs extensively rotate, shift, and deform for nicking and hairpin formation. Two intertwined RAG1 subunits crisscross four times between the asymmetric pair of severely bent 12/23-RSS DNAs. Location-sensitive bending of 60° and 150° in 12- and 23-RSS spacers, respectively, must occur for RAG1/2 to capture the nonamers and pair the heptamers for symmetric double-strand breakage. DNA pairing is thus sequence-context dependent and structure specific, which partly explains the "beyond 12/23" restriction. Finally, catalysis in crystallo reveals the process of DNA hairpin formation and its stabilization by interleaved base stacking.

PubMed: 29628308
DOI: 10.1016/j.molcel.2018.03.008

実験手法

ELECTRON MICROSCOPY (3.17 Å)