Evidence map›Paper›PMID 26548953›Full record

ArticleCell2015

Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures.

Heng Ru, Melissa G Chambers, Tian-Min Fu, Alexander B Tong, Maofu Liao, Hao Wu

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

134 citing papers in PubMed, 196 citations in OpenAlex.

  1. Article
  2. Article
  3. HMGB1 as a danger signal in vascular remodeling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
    Review
  4. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Article

74 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Heng RuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Melissa G ChambersDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Tian-Min FuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Alexander B TongDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Maofu LiaoDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: maofu_liao@hms.harvard.edu.
Hao WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: wu@crystal.harvard.edu.
Boston Children's Hospital · USHarvard University · US

Funding

Structural & Functional Studies of TLR/IL-1R SignalingR37AI050872 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2012 to 2021
$4.7M
Molecular mechanisms of the RAG recombinase in V(D)J recombination and diseaseR01AI125535 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2016 to 2020
$3.2M
NIAID NIH HHS R01 AI125535NIAID NIH HHS R37 AI050872
6 · The paper itself

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.

Indexed as

V(D)J RecombinationAmino Acid SequenceAnimalsCryoelectron MicroscopyDNA-Binding ProteinsHomeodomain ProteinsHumansMiceMolecular Sequence DataMultiprotein ComplexesMutationSequence AlignmentZebrafishDNA-Binding ProteinsHomeodomain ProteinsMultiprotein ComplexesRAG-1 proteinV(D)J recombination activating protein 2

Identifiers

PMID26548953
PMCPMC4690471
OpenAlexW2192556660

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.