Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 122, Issue 31, Page e2512362122, Year 2025
Publish date	Aug 5, 2025
Authors	Xuemin Chen / Liangrui Yao / Wenwen Li / Shanshan Ma / Xingyun Yuan / Yang Yang / Yuan Yuan / Yumei Liu / Lan Liu / Huaibin Wang / Martin Gellert / Wei Yang /
PubMed Abstract	The recombination activating genes 1 and 2 (RAG1/2) recombinase, which initiates V(D)J recombination in jawed vertebrates, evolved from RNaseH-like transposases such as Transib and ProtoRAG. However, ...The recombination activating genes 1 and 2 (RAG1/2) recombinase, which initiates V(D)J recombination in jawed vertebrates, evolved from RNaseH-like transposases such as Transib and ProtoRAG. However, its postcleavage transposase activity is strictly suppressed. Previous structural studies have focused only on the conserved core domains of RAG1/2, leaving the regulatory mechanisms of the noncore regions unclear. To investigate how RAG1/2 suppresses transposition and regulates DNA cleavage, we determined cryo-electron microscopy (cryo-EM) structures of nearly full-length RAG1/2 complexed with cleaved recombination signal sequences (RSS) in a signal-end complex (SEC) at resolutions up to 2.95 Å. Two key structures, SEC-0 and SEC-Plant Homeodomain (PHD), reveal distinct regulatory roles of RAG2, which is absent in Transib transposase. SEC-0 displays a closed conformation, revealing that the core RAG2 facilitates sequential DNA cleavage by stabilizing the RSS-cleaved states in a "spring-loaded" mechanism. SEC-PHD reveals how RAG2's noncore PHD and Acidic Hinge (AH), which are absent in ProtoRAG, inhibit target DNA binding in transposition. Histone H3K4me3, which recruits RAG1/2 to RSS sites, does not influence RAG1/2 binding to V, D, or J gene segments bordered by RSS. In contrast, the suppressed transposition can be activated by H3K4me3 peptides that dislodge the inhibitory PHD. To achieve this derepression in vivo, however, would require an unlikely close placement of two nucleosomes flanking a target DNA bent by nearly 180°. Our structural and biochemical results elucidate how RAG1 has acquired RAG2 and utilizes its core and noncore domains to enhance V(D)J recombination and suppress transposition.
External links	Proc Natl Acad Sci U S A / PubMed:40729386 / PubMed Central
Methods	EM (single particle)
Resolution	2.95 - 3.43 Å
Structure data	61715 9jpu EMDB-61715, PDB-9jpu: CryoEM structure of mouse RAG SEC-PHD Method: EM (single particle) / Resolution: 3.25 Å 61717 9jpx EMDB-61717, PDB-9jpx: CryoEM structure of mouse RAG SEC-0 Method: EM (single particle) / Resolution: 2.95 Å 61730 9jqn EMDB-61730, PDB-9jqn: CryoEM structure of mouse RAG SEC-2DNA Method: EM (single particle) / Resolution: 3.03 Å 61816 9jts EMDB-61816, PDB-9jts: CryoEM structure of mouse RAG SEC-1DNA (12RSS side) Method: EM (single particle) / Resolution: 3.36 Å 61817 9jtu EMDB-61817, PDB-9jtu: CryoEM structure of mouse RAG SEC-1DNA (23RSS side) Method: EM (single particle) / Resolution: 3.43 Å
Chemicals	ChemComp-CA: Unknown entry ChemComp-ZN: Unknown entry ChemComp-HOH: WATER
Source	mus musculus (house mouse) escherichia coli (E. coli)
Keywords	DNA BINDING PROTEIN/DNA / V(D)J recombination / RAG / PHD / Transposition / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex