[English] 日本語
Yorodumi
- EMDB-63291: Structure of human dimeric NLRP7-TCL1A complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-63291
TitleStructure of human dimeric NLRP7-TCL1A complex
Map data
Sample
  • Complex: Structure of human dimer NLRP7-TCL1A complex
    • Protein or peptide: Isoform 3 of NACHT, LRR and PYD domains-containing protein 7
    • Protein or peptide: T-cell leukemia/lymphoma protein 1A
Keywordssubcortical maternal complex / SIGNALING PROTEIN
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)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.58 Å
AuthorsLiu QT / Li JH
Funding support China, 1 items
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, 2025-
Header (metadata) releaseDec 10, 2025-
Map releaseDec 10, 2025-
UpdateApr 15, 2026-
Current statusApr 15, 2026Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_63291.png

Downloads & links

-
Map

FileDownload / File: emd_63291.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 256 pix.
= 281.6 Å		1.1 Å/pix.
x 256 pix.
= 281.6 Å		1.1 Å/pix.
x 256 pix.
= 281.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.3139812 - 0.6174438
Average (Standard dev.)0.0011928128 (±0.017934935)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 281.6 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_63291_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_63291_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Structure of human dimer NLRP7-TCL1A complex

EntireName: Structure of human dimer NLRP7-TCL1A complex
Components
  • Complex: Structure of human dimer NLRP7-TCL1A complex
    • Protein or peptide: Isoform 3 of NACHT, LRR and PYD domains-containing protein 7
    • Protein or peptide: T-cell leukemia/lymphoma protein 1A

-
Supramolecule #1: Structure of human dimer NLRP7-TCL1A complex

SupramoleculeName: Structure of human dimer NLRP7-TCL1A complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Isoform 3 of NACHT, LRR and PYD domains-containing protein 7

MacromoleculeName: Isoform 3 of NACHT, LRR and PYD domains-containing protein 7
type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 118.448906 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MTSPQLEWTL QTLLEQLNED ELKSFKSLLW AFPLEDVLQK TPWSEVEEAD GKKLAEILVN TSSENWIRNA TVNILEEMNL TELCKMAKA EMMEDGQVQE IDNPELGDAE EDSELAKPGE KEGWRNSMEK QSLVWKNTFW QGDIDNFHDD VTLRNQRFIP F LNPRTPRK ...String:
MTSPQLEWTL QTLLEQLNED ELKSFKSLLW AFPLEDVLQK TPWSEVEEAD GKKLAEILVN TSSENWIRNA TVNILEEMNL TELCKMAKA EMMEDGQVQE IDNPELGDAE EDSELAKPGE KEGWRNSMEK QSLVWKNTFW QGDIDNFHDD VTLRNQRFIP F LNPRTPRK LTPYTVVLHG PAGVGKTTLA KKCMLDWTDC NLSPTLRYAF YLSCKELSRM GPCSFAELIS KDWPELQDDI PS ILAQAQR ILFVVDGLDE LKVPPGALIQ DICGDWEKKK PVPVLLGSLL KRKMLPRAAL LVTTRPRALR DLQLLAQQPI YVR VEGFLE EDRRAYFLRH FGDEDQAMRA FELMRSNAAL FQLGSAPAVC WIVCTTLKLQ MEKGEDPVPT CLTRTGLFLR FLCS RFPQG AQLRGALRTL SLLAAQGLWA QMSVFHREDL ERLGVQESDL RLFLDGDILR QDRVSKGCYS FIHLSFQQFL TALFY ALEK EEGEDRDGHA WDIGDVQKLL SGEERLKNPD LIQVGHFLFG LANEKRAKEL EATFGCRMSP DIKQELLQCK AHLHAN KPL SVTDLKEVLG CLYESQEEEL AKVVVAPFKE ISIHLTNTSE VMHCSFSLKH CQDLQKLSLQ VAKGVFLENY MDFELDI EF ERCTYLTIPN WARQDLRSLR LWTDFCSLFS SNSNLKFLEV KQSFLSDSSV RILCDHVTRS TCHLQKVEIK NVTPDTAY R DFCLAFIGKK TLTHLTLAGH IEWERTMMLM LCDLLRNHKC NLQYLRLGGH CATPEQWAEF FYVLKANQSL KHLRLSANV LLDEGAMLLY KTMTRPKHFL QMLSLENCRL TEASCKDLAA VLVVSKKLTH LCLAKNPIGD TGVKFLCEGL SYPDCKLQTL VLQQCSITK LGCRYLSEAL QEACSLTNLD LSINQIARGL WILCQALENP NCNLKHLRLW SCSLMPFYCQ HLGSALLSNQ K LETLDLGQ NHLWKSGIIK LFGVLRQRTG SLKILRLKTY ETNLEIKKLL EEVKEKNPKL TIDCNASGAT APPCCDFFC

UniProtKB: NACHT, LRR and PYD domains-containing protein 7

-
Macromolecule #2: T-cell leukemia/lymphoma protein 1A

MacromoleculeName: T-cell leukemia/lymphoma protein 1A / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.67258 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EAVTDHPDRL WAWEKFVYLD EKQHAWLPLT IEIKDRLQLR VLLRREDVVL GRPMTPTQIG PSLLPIMWQL YPDGRYRSSD SSFWRLVYH IKIDGVEDML LELLPDD

UniProtKB: T-cell leukemia/lymphoma protein 1A

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration2.3 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
150.0 mMNaClsodium chloride
25.0 mMHepes4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
5.0 mMDTTDithiothreitol

Details: 25mM Hepes pH 7.5, 150mM NaCl,5 mM DTT
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: Vitrification carried out in argon atmosphere.
DetailsThis sample was monodisperse

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 51.36 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.1 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1195156
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

+
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