6B40

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

6B40 の概要

• エントリーDOI: 10.2210/pdb6b40/pdb
• EMDBエントリー: 7046 7077 7078
• 分子名称: RAG1L,RAG1L, 31TIR intact strand, 31TIR pre-nicked strand of signal DNA, ... (7 entities in total)
• 機能のキーワード: dna transposase, dna cut and paste transposition, dde family rnase h fold dna transposase, recombination
• 由来する生物種: Branchiostoma belcheri (Amphioxus); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 304464.73

構造登録者

Zhang, Y.,Cheng, T.C.,Xiong, Y.,Schatz, D.G. (登録日: 2017-09-25, 公開日: 2019-03-20, 最終更新日: 2024-03-13)

主引用文献

Zhang, Y.,Cheng, T.C.,Huang, G.,Lu, Q.,Surleac, M.D.,Mandell, J.D.,Pontarotti, P.,Petrescu, A.J.,Xu, A.,Xiong, Y.,Schatz, D.G.
Transposon molecular domestication and the evolution of the RAG recombinase.
Nature, 569:79-84, 2019

PubMed Abstract: 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.

PubMed: 30971819
DOI: 10.1038/s41586-019-1093-7

実験手法

ELECTRON MICROSCOPY (4.3 Å)