[English] 日本語
Yorodumi
- PDB-9b83: Cryo-EM structure of human ADAR1 in complex with dsRNA derived fr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9b83
TitleCryo-EM structure of human ADAR1 in complex with dsRNA derived from human GLI1 gene
Components
  • Maltodextrin-binding protein,Double-stranded RNA-specific adenosine deaminase
  • RNA (31-MER)
KeywordsHYDROLASE/RNA / ADAR1-dsRNA complex / HYDROLASE-RNA complex
Function / homology
Function and homology information


somatic diversification of immune receptors via somatic mutation / negative regulation of post-transcriptional gene silencing by regulatory ncRNA / C6 deamination of adenosine / Formation of editosomes by ADAR proteins / supraspliceosomal complex / double-stranded RNA adenine deaminase / tRNA-specific adenosine deaminase activity / adenosine to inosine editing / negative regulation of protein kinase activity by regulation of protein phosphorylation / double-stranded RNA adenosine deaminase activity ...somatic diversification of immune receptors via somatic mutation / negative regulation of post-transcriptional gene silencing by regulatory ncRNA / C6 deamination of adenosine / Formation of editosomes by ADAR proteins / supraspliceosomal complex / double-stranded RNA adenine deaminase / tRNA-specific adenosine deaminase activity / adenosine to inosine editing / negative regulation of protein kinase activity by regulation of protein phosphorylation / double-stranded RNA adenosine deaminase activity / base conversion or substitution editing / response to interferon-alpha / hematopoietic stem cell homeostasis / adenosine deaminase activity / RISC complex assembly / pre-miRNA processing / negative regulation of hepatocyte apoptotic process / definitive hemopoiesis / negative regulation of type I interferon-mediated signaling pathway / hepatocyte apoptotic process / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / positive regulation of viral genome replication / RNA processing / hematopoietic progenitor cell differentiation / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / protein export from nucleus / erythrocyte differentiation / PKR-mediated signaling / response to virus / cellular response to virus / mRNA processing / protein import into nucleus / osteoblast differentiation / Interferon alpha/beta signaling / double-stranded RNA binding / outer membrane-bounded periplasmic space / defense response to virus / innate immune response / nucleolus / mitochondrion / DNA binding / RNA binding / nucleoplasm / metal ion binding / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
ADAR1, first double-stranded RNA binding domain / ADAR1, third double-stranded RNA binding domain / Z-DNA-binding domain in adenosine deaminases. / Z-binding domain / Adenosine deaminase z-alpha domain / Z-binding domain profile. / Adenosine deaminase/editase / Adenosine-deaminase (editase) domain / Adenosine to inosine editase domain profile. / tRNA-specific and double-stranded RNA adenosine deaminase (RNA-specific editase) ...ADAR1, first double-stranded RNA binding domain / ADAR1, third double-stranded RNA binding domain / Z-DNA-binding domain in adenosine deaminases. / Z-binding domain / Adenosine deaminase z-alpha domain / Z-binding domain profile. / Adenosine deaminase/editase / Adenosine-deaminase (editase) domain / Adenosine to inosine editase domain profile. / tRNA-specific and double-stranded RNA adenosine deaminase (RNA-specific editase) / Double-stranded RNA binding motif / Double-stranded RNA binding motif / Double stranded RNA-binding domain (dsRBD) profile. / Double-stranded RNA-binding domain / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
INOSITOL HEXAKISPHOSPHATE / RNA / RNA (> 10) / Maltodextrin-binding protein / Double-stranded RNA-specific adenosine deaminase
Similarity search - Component
Biological speciesEscherichia coli (E. coli)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.01 Å
AuthorsDeng, X. / Gao, Y.
Funding support United States, 1items
OrganizationGrant numberCountry
Cancer Prevention and Research Institute of Texas (CPRIT)RP190602 United States
CitationJournal: Mol Cell / Year: 2025
Title: Biochemical profiling and structural basis of ADAR1-mediated RNA editing.
Authors: Xiangyu Deng / Lina Sun / Min Zhang / Rashmi Basavaraj / Jin Wang / Yi-Lan Weng / Yang Gao /
Abstract: ADAR1 regulates RNA-induced immune responses by converting adenosine to inosine in double-stranded RNA. Mutations in ADAR1 are associated with human autoimmune disease, and targeting ADAR1 has been ...ADAR1 regulates RNA-induced immune responses by converting adenosine to inosine in double-stranded RNA. Mutations in ADAR1 are associated with human autoimmune disease, and targeting ADAR1 has been proposed for cancer immunotherapy. However, the molecular mechanisms underlying ADAR1-mediated editing remain unclear. Here, we provide detailed biochemical and structural characterizations of human ADAR1. Our biochemical profiling reveals that ADAR1 editing is both sequence and RNA-duplex-length dependent but can well tolerate mismatches near the editing site. High-resolution ADAR1-RNA complex structures, combined with mutagenesis, elucidate RNA binding, substrate selection, dimerization, and the essential role of RNA-binding domain 3. The ADAR1 structures also help explain the potential defects of disease-associated mutations, where biochemical and RNA sequencing analysis further indicate some of the mutations preferentially impact the editing of RNAs with short duplexes. These findings unveil the molecular basis of ADAR1 editing and provide insights into its immune-regulatory functions and therapeutic potential.
History
DepositionMar 28, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 26, 2025Provider: repository / Type: Initial release
Revision 1.1Apr 2, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update
Revision 1.2Apr 16, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: RNA (31-MER)
A: Maltodextrin-binding protein,Double-stranded RNA-specific adenosine deaminase
B: Maltodextrin-binding protein,Double-stranded RNA-specific adenosine deaminase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)344,6489
Polymers343,0663
Non-polymers1,5826
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: RNA chain RNA (31-MER)


Mass: 12563.527 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#2: Protein Maltodextrin-binding protein,Double-stranded RNA-specific adenosine deaminase / DRADA / 136 kDa double-stranded RNA-binding protein / p136 / Interferon-inducible protein 4 / IFI-4 / K88DSRBP


Mass: 165251.234 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human)
Gene: malE, malE_1, A9X72_23600, ACN81_05700, ACU57_23670, AM464_13530, B6R31_000964, BANRA_05111, BCB93_001091, BF481_003801, BG944_002391, BGM66_004246, BJI68_06200, BJJ90_24825, BK292_00970, BTB68_ ...Gene: malE, malE_1, A9X72_23600, ACN81_05700, ACU57_23670, AM464_13530, B6R31_000964, BANRA_05111, BCB93_001091, BF481_003801, BG944_002391, BGM66_004246, BJI68_06200, BJJ90_24825, BK292_00970, BTB68_002078, BTQ06_17300, BvCmsKKP061_03224, BvCmsSIP010_04050, C0P57_003867, C1Q91_002164, C2R31_001890, C3F40_15210, C9E67_28370, CA593_05740, CF22_001770, CG692_11710, CG704_16590, CG831_003746, CIG67_12040, CQ986_003892, CR538_23895, CR539_01985, CTR35_003815, CV83915_02005, D4M65_12865, DIV22_28370, DNX30_07695, DS732_01860, DTL43_19585, E4K51_08355, E5H86_20640, E6D34_15030, EAI46_20350, EC95NR1_03574, ECs5017, EIZ93_13775, EN85_000970, EPS97_17355, ExPECSC038_04540, F9407_08085, F9461_21760, FIJ20_18085, FJQ40_13885, FOI11_015465, FOI11_20215, FPS11_04610, FV293_00135, FWK02_22115, G3V95_18070, G4A38_02205, G4A47_04495, G9448_13225, GAI89_05080, GAJ12_13200, GJ11_25475, GKF66_19285, GNW61_17855, GOP25_18965, GP965_07770, GP975_07695, GP979_10140, GQA06_09595, GQM04_22095, GQM21_08325, GRW05_14255, GRW24_12940, GRW56_08975, GRW57_10345, GUC01_08260, H0O72_20100, HEP30_015080, HHH44_003952, HLX92_13085, HMV95_14740, HV109_22180, HV209_20940, HVW43_14700, HVY77_23840, HX086_10250, HX136_23390, I6H00_16895, I6H02_15990, J0541_001933, J5U05_001620, JNP96_01525, KV259_002584, KV317_002918, KV371_002846, KV406_003109, KV449_002737, KV455_002759, KV463_002918, KV469_002607, KV499_002898, KV500_002927, NCTC10418_07064, NCTC10429_00012, NCTC10865_05806, NCTC11126_02082, NCTC11181_01902, NCTC12950_05149, NCTC13148_04480, NCTC4450_01671, NCTC8009_08341, NCTC8179_05034, NCTC8333_05503, NCTC8500_05253, NCTC8622_01707, NCTC8960_02276, NCTC8985_03950, NCTC9706_01951, NCTC9962_03706, NEP60_16880, O5851_07355, RG28_25590, SAMEA3752557_02201, TUM18780_41180, WR15_07725, ADAR, ADAR1, DSRAD, G1P1, IFI4
Production host: Homo sapiens (human)
References: UniProt: C3SHQ8, UniProt: P55265, double-stranded RNA adenine deaminase
#3: Chemical ChemComp-IHP / INOSITOL HEXAKISPHOSPHATE / MYO-INOSITOL HEXAKISPHOSPHATE / INOSITOL 1,2,3,4,5,6-HEXAKISPHOSPHATE


Mass: 660.035 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C6H18O24P6
#4: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: human ADAR1 in complex with dsRNA derived from human GLI1 gene
Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

MicroscopyModel: FEI TECNAI 20
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 600 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM softwareName: PHENIX / Version: 1.20.1_4487: / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42348 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0046595
ELECTRON MICROSCOPYf_angle_d0.6829050
ELECTRON MICROSCOPYf_dihedral_angle_d9.3481169
ELECTRON MICROSCOPYf_chiral_restr0.0451029
ELECTRON MICROSCOPYf_plane_restr0.0061016

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more