6B40

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

Summary for 6B40

• Entry DOI: 10.2210/pdb6b40/pdb
• EMDB information: 7046 7077 7078
• Descriptor: RAG1L,RAG1L, 31TIR intact strand, 31TIR pre-nicked strand of signal DNA, ... (7 entities in total)
• Functional Keywords: dna transposase, dna cut and paste transposition, dde family rnase h fold dna transposase, recombination
• Biological source: Branchiostoma belcheri (Amphioxus); More
• Total number of polymer chains: 10
• Total formula weight: 304464.73

Authors

Zhang, Y.,Cheng, T.C.,Xiong, Y.,Schatz, D.G. (deposition date: 2017-09-25, release date: 2019-03-20, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (4.3 Å)