[English] 日本語
Yorodumi
- PDB-9lq2: Structure of human dimeric NLRP7-TCL1A complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9lq2
TitleStructure of human dimeric NLRP7-TCL1A complex
Components
  • Isoform 3 of NACHT, LRR and PYD domains-containing protein 7
  • T-cell leukemia/lymphoma protein 1A
KeywordsSIGNALING PROTEIN / subcortical maternal complex
Function / homology
Function and homology information


interleukin-1 binding / caspase binding / aspartic-type endopeptidase inhibitor activity / negative regulation of protein processing / negative regulation of interleukin-1 beta production / cellular response to interleukin-1 / negative regulation of cytokine production involved in inflammatory response / protein serine/threonine kinase activator activity / cellular response to lipopolysaccharide / regulation of inflammatory response ...interleukin-1 binding / caspase binding / aspartic-type endopeptidase inhibitor activity / negative regulation of protein processing / negative regulation of interleukin-1 beta production / cellular response to interleukin-1 / negative regulation of cytokine production involved in inflammatory response / protein serine/threonine kinase activator activity / cellular response to lipopolysaccharide / regulation of inflammatory response / intracellular signal transduction / protein kinase binding / endoplasmic reticulum / nucleoplasm / ATP binding / identical protein binding / nucleus / cytoplasm / cytosol
Similarity search - Function
TCL1/MTCP1 / TCL1/MTCP1 superfamily / TCL1/MTCP1 family / : / NACHT, LRR and PYD domains-containing protein, helical domain HD2 / NLRC4 helical domain HD2 / NOD2, winged helix domain / NOD2 winged helix domain / NACHT nucleoside triphosphatase / NACHT domain ...TCL1/MTCP1 / TCL1/MTCP1 superfamily / TCL1/MTCP1 family / : / NACHT, LRR and PYD domains-containing protein, helical domain HD2 / NLRC4 helical domain HD2 / NOD2, winged helix domain / NOD2 winged helix domain / NACHT nucleoside triphosphatase / NACHT domain / NACHT-NTPase domain profile. / DAPIN domain profile. / DAPIN domain / PAAD/DAPIN/Pyrin domain / PAAD/DAPIN/Pyrin domain / Leucine rich repeat, ribonuclease inhibitor type / Leucine Rich repeat / Death-like domain superfamily / Leucine-rich repeat / Leucine-rich repeat domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
T-cell leukemia/lymphoma protein 1A / NACHT, LRR and PYD domains-containing protein 7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.58 Å
AuthorsLiu, Q.T. / Li, J.H.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2026
Title: TCL1A mediates DNA methylation defects in recurrent hydatidiform mole with NLRP7 pathogenic variants.
Authors: Zheng Gao / Qingting Liu / Lei Li / Ting Hu / Xukun Lu / Yu Wu / Dandan Qin / Xiaoxiao Wang / Chen Gu / Jinhong Li / Chengpeng Xu / Dan Zhou / Fan Zhou / YanLing Bai / Xiangjin Kang / ...Authors: Zheng Gao / Qingting Liu / Lei Li / Ting Hu / Xukun Lu / Yu Wu / Dandan Qin / Xiaoxiao Wang / Chen Gu / Jinhong Li / Chengpeng Xu / Dan Zhou / Fan Zhou / YanLing Bai / Xiangjin Kang / Jianqiao Liu / Dong Deng / Lei Li /
Abstract: Pathogenic variants in NLRP7, implicated in 55% of recurrent hydatidiform mole characterized by hypomethylation at maternally methylated imprinted regions, are proposed to disrupt de novo DNA ...Pathogenic variants in NLRP7, implicated in 55% of recurrent hydatidiform mole characterized by hypomethylation at maternally methylated imprinted regions, are proposed to disrupt de novo DNA methylation in human oocytes. However, the precise mechanism remains unclear. Here, we identify TCL1A, a DNMT3A inhibitor, as an endogenous NLRP7-interacting partner. The cryo-EM structure of the NLRP7-TCL1A complex reveals its fundamental architecture. Comprehensive analysis demonstrates that the majority of recurrent hydatidiform mole-causing NLRP7 variants impair its interaction with TCL1A. Mechanistically, NLRP7 potentially safeguards oocyte methylome by sequestering TCL1A in the cytoplasm, thereby preventing its nuclear entry and subsequent suppression of DNMT3A-mediated de novo methylation. Combining in silico predictions and interaction analysis, we identify L766R as a pathogenic variant. These findings propose a cytoplasmic regulatory mechanism governing nuclear DNA methylation, explaining the hypomethylation pathogenesis in NLRP7 variant-associated recurrent hydatidiform mole.
History
DepositionJan 27, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Dec 10, 2025Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Dec 10, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Apr 15, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update
Revision 2.0Apr 15, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform 3 of NACHT, LRR and PYD domains-containing protein 7
B: Isoform 3 of NACHT, LRR and PYD domains-containing protein 7
D: T-cell leukemia/lymphoma protein 1A
E: T-cell leukemia/lymphoma protein 1A
F: T-cell leukemia/lymphoma protein 1A
G: T-cell leukemia/lymphoma protein 1A


Theoretical massNumber of molelcules
Total (without water)287,5886
Polymers287,5886
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein Isoform 3 of NACHT, LRR and PYD domains-containing protein 7 / Nucleotide-binding oligomerization domain protein 12 / PYRIN-containing APAF1-like protein 3


Mass: 118448.906 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NLRP7, NALP7, NOD12, PYPAF3 / Production host: Homo sapiens (human) / References: UniProt: Q8WX94
#2: Protein
T-cell leukemia/lymphoma protein 1A / Oncogene TCL-1 / Oncogene TCL1 / Protein p14 TCL1


Mass: 12672.580 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TCL1A, TCL1 / Production host: Homo sapiens (human) / References: UniProt: P56279
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Structure of human dimer NLRP7-TCL1A complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5 / Details: 25mM Hepes pH 7.5, 150mM NaCl,5 mM DTT
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMsodium chlorideNaCl1
225 mM4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidHepes1
35 mMDithiothreitolDTT1
SpecimenConc.: 2.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: Vitrification carried out in argon atmosphere

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1100 nm
Image recordingElectron dose: 51.36 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1195156 / Symmetry type: POINT
RefinementHighest resolution: 3.58 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0116792
ELECTRON MICROSCOPYf_angle_d0.86622737
ELECTRON MICROSCOPYf_dihedral_angle_d3.8172196
ELECTRON MICROSCOPYf_chiral_restr0.0372565
ELECTRON MICROSCOPYf_plane_restr0.0032878

+
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