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- EMDB-66203: Structure of dimeric mouse NLRP14-KDM2A-SKP1 complex -

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Basic information

Entry
Database: EMDB / ID: EMD-66203
TitleStructure of dimeric mouse NLRP14-KDM2A-SKP1 complex
Map data
Sample
  • Complex: Dimeric mouse NLRP14-KDM2A-SKP1 complex
    • Protein or peptide: Lysine-specific demethylase 2A
    • Protein or peptide: S-phase kinase-associated protein 1
    • Protein or peptide: NACHT, LRR and PYD domains-containing protein 14
KeywordsCryo-EM / complex / NLRP14 / KDM2A / SKP1 / early embryonic development / CYTOSOLIC PROTEIN
Function / homology
Function and homology information


Prolactin receptor signaling / [histone H3]-dimethyl-L-lysine36 demethylase / histone H3K36me/H3K36me2 demethylase activity / HDMs demethylate histones / SCF-beta-TrCP mediated degradation of Emi1 / Regulation of BACH1 activity / SCF(Skp2)-mediated degradation of p27/p21 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Regulation of RUNX2 expression and activity ...Prolactin receptor signaling / [histone H3]-dimethyl-L-lysine36 demethylase / histone H3K36me/H3K36me2 demethylase activity / HDMs demethylate histones / SCF-beta-TrCP mediated degradation of Emi1 / Regulation of BACH1 activity / SCF(Skp2)-mediated degradation of p27/p21 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Regulation of RUNX2 expression and activity / Degradation of GLI1 by the proteasome / Cyclin D associated events in G1 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Orc1 removal from chromatin / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Dectin-1 mediated noncanonical NF-kB signaling / NIK-->noncanonical NF-kB signaling / Degradation of beta-catenin by the destruction complex / Activation of NF-kappaB in B cells / Iron uptake and transport / FCERI mediated NF-kB activation / CLEC7A (Dectin-1) signaling / Interleukin-1 signaling / neuroepithelial cell differentiation / F-box domain binding / Downstream TCR signaling / histone H3K36 demethylase activity / GLI3 is processed to GLI3R by the proteasome / unmethylated CpG binding / PcG protein complex / Regulation of PLK1 Activity at G2/M Transition / : / Neddylation / gap junction / maintenance of protein location in nucleus / Cul7-RING ubiquitin ligase complex / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of epithelial cell apoptotic process / ubiquitin ligase activator activity / SCF ubiquitin ligase complex / heart looping / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / histone demethylase activity / cullin family protein binding / protein monoubiquitination / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / molecular function activator activity / transcription initiation-coupled chromatin remodeling / transcription coregulator activity / circadian regulation of gene expression / neural tube closure / regulation of circadian rhythm / beta-catenin binding / double-strand break repair via nonhomologous end joining / multicellular organism growth / neuron differentiation / protein polyubiquitination / regulation of inflammatory response / spermatogenesis / in utero embryonic development / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / cell differentiation / protein ubiquitination / chromatin remodeling / protein domain specific binding / negative regulation of gene expression / apoptotic process / positive regulation of gene expression / regulation of transcription by RNA polymerase II / centrosome / negative regulation of apoptotic process / chromatin / zinc ion binding / nucleoplasm / ATP binding / nucleus / cytoplasm / cytosol
Similarity search - Function
PHD-finger / Jumonji, helical domain / Jumonji helical domain / : / : / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / NACHT, LRR and PYD domains-containing protein, helical domain HD2 / NLRC4 helical domain HD2 / NOD2, winged helix domain ...PHD-finger / Jumonji, helical domain / Jumonji helical domain / : / : / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / NACHT, LRR and PYD domains-containing protein, helical domain HD2 / NLRC4 helical domain HD2 / NOD2, winged helix domain / NOD2 winged helix domain / CXXC zinc finger domain / Zinc finger, CXXC-type / Zinc finger CXXC-type profile. / NACHT nucleoside triphosphatase / NACHT domain / NACHT-NTPase domain profile. / F-box-like / SKP1 component, dimerisation / S-phase kinase-associated protein 1 / SKP1-like, dimerisation domain superfamily / Skp1 family, dimerisation domain / F-box domain / Leucine rich repeat, ribonuclease inhibitor type / Leucine Rich repeat / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / A domain family that is part of the cupin metalloenzyme superfamily. / JmjC domain / JmjC domain profile. / Zinc finger, PHD-type, conserved site / Zinc finger PHD-type signature. / SKP1/BTB/POZ domain superfamily / Zinc finger PHD-type profile. / Leucine-rich repeat / Zinc finger, PHD-finger / Zinc finger, PHD-type / PHD zinc finger / Zinc finger, FYVE/PHD-type / Leucine-rich repeat domain superfamily / Zinc finger, RING/FYVE/PHD-type / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Lysine-specific demethylase 2A / NACHT, LRR and PYD domains-containing protein 14 / S-phase kinase-associated protein 1
Similarity search - Component
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.35 Å
AuthorsLiu S / Jiao H / Yan L / Qi Q / Chi P / Lu Y / Li JH / Li JL / Ju S / Wang X ...Liu S / Jiao H / Yan L / Qi Q / Chi P / Lu Y / Li JH / Li JL / Ju S / Wang X / Hu H / Deng D
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31971132 China
CitationJournal: Nat Commun / Year: 2026
Title: NLRP14 modulates the activity of E3 ubiquitin ligases during the oocyte-to-embryo transition.
Authors: Sibei Liu / Qianqian Qi / Pengliang Chi / Haizhan Jiao / Li Yan / Yuechao Lu / Rongrong Zhang / Jinhong Li / Sicheng Ju / Zhuo Han / Zihan Zhang / Qingting Liu / Guojin Ou / Jialu Li / Jing ...Authors: Sibei Liu / Qianqian Qi / Pengliang Chi / Haizhan Jiao / Li Yan / Yuechao Lu / Rongrong Zhang / Jinhong Li / Sicheng Ju / Zhuo Han / Zihan Zhang / Qingting Liu / Guojin Ou / Jialu Li / Jing Chen / Xiang Wang / Lei Li / Li Guo / Xue Jiao / Hongli Hu / Yongmei Jiang / Dong Deng /
Abstract: NLRP14 is an essential maternal factor for mammalian embryonic development. Maternal ablation of NLRP14 in mice impairs DNA demethylation and calcium homeostasis in zygotes, causing early embryonic ...NLRP14 is an essential maternal factor for mammalian embryonic development. Maternal ablation of NLRP14 in mice impairs DNA demethylation and calcium homeostasis in zygotes, causing early embryonic arrest. However, the underlying biochemical events remain largely unknown. Here, we identified two binding partners (KDM2A and UHRF1) of NLRP14 and further solved structures of NLRP14-KDM2A-SKP1 and NLRP14-UHRF1. Structural analysis revealed that NLRP14 modulates the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase and the RING-type E3 ubiquitin ligase UHRF1 through two distinct mechanisms. Mechanistically, NLRP14 competitively inhibits KDM2A-mediated SCF assembly or allosterically inhibits the activity of UHRF1 by occupying the E2 ubiquitin-conjugating enzyme (UBE2D) binding site of the ubiquitin-like (UBL) domain. Deletion of NLRP14 in mice increases ubiquitination levels in oocytes during maturation and after fertilization. Collectively, our findings identify NLRP14 as a dual regulator that restrains E3 ubiquitin ligase-driven ubiquitination by limiting SCF complex assembly and attenuating UHRF1 activity. This regulatory role is required to prevent excessive protein ubiquitination and maintain proteostasis during the oocyte-to-embryo transition, thereby supporting early embryonic development. Our study uncovers maternal regulation of proteostasis in oocytes and suggests that dysregulating proteostasis is an important factor in the pathogenesis of reproductive disorders.
History
DepositionSep 15, 2025-
Header (metadata) releaseMar 18, 2026-
Map releaseMar 18, 2026-
UpdateApr 22, 2026-
Current statusApr 22, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_66203.png

Downloads & links

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Map

FileDownload / File: emd_66203.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 360 pix.
= 306. Å		0.85 Å/pix.
x 360 pix.
= 306. Å		0.85 Å/pix.
x 360 pix.
= 306. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.084
Minimum - Maximum-0.08223146 - 0.64139485
Average (Standard dev.)0.0034727484 (±0.017631836)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 306.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Dimeric mouse NLRP14-KDM2A-SKP1 complex

EntireName: Dimeric mouse NLRP14-KDM2A-SKP1 complex
Components
  • Complex: Dimeric mouse NLRP14-KDM2A-SKP1 complex
    • Protein or peptide: Lysine-specific demethylase 2A
    • Protein or peptide: S-phase kinase-associated protein 1
    • Protein or peptide: NACHT, LRR and PYD domains-containing protein 14

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Supramolecule #1: Dimeric mouse NLRP14-KDM2A-SKP1 complex

SupramoleculeName: Dimeric mouse NLRP14-KDM2A-SKP1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: Lysine-specific demethylase 2A

MacromoleculeName: Lysine-specific demethylase 2A / type: protein_or_peptide / ID: 1 / Details: KDM2A fused Strep tag at the N-terminal / Number of copies: 2 / Enantiomer: LEVO / EC number: [histone H3]-dimethyl-L-lysine36 demethylase
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 40.626574 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MWSHPQFEKG TIVPKLQAIT ASSANLRPNP RVLMQHCPAR NPQHGDEEGL GGEEEEEEEE EEDDSAEEGG AARLNGRGSW AQDGDESWM QREVWMSVFR YLSRKELCEC MRVCKTWYKW CCDKRLWTKI DLSRCKAIVP QALSGIIKRQ PVSLDLSWTN I SKKQLTWL ...String:
MWSHPQFEKG TIVPKLQAIT ASSANLRPNP RVLMQHCPAR NPQHGDEEGL GGEEEEEEEE EEDDSAEEGG AARLNGRGSW AQDGDESWM QREVWMSVFR YLSRKELCEC MRVCKTWYKW CCDKRLWTKI DLSRCKAIVP QALSGIIKRQ PVSLDLSWTN I SKKQLTWL VNRLPGLKDL LLAGCSWSAV SALSTSSCPL LRTLDLRWAV GIKDPQIRDL LTPPTDKPGQ DNRSKLRNMT DF RLAGLDI TDATLRLIIR HMPLLSRLDL SHCSHLTDQS SNLLTAVGSS TRYSLTELNM AGCNKLTDQT LFFLRRIANV TLI DLRGCK QITRKACEHF ISDLSINSLY CLSDEKLIQK IS

UniProtKB: Lysine-specific demethylase 2A

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Macromolecule #2: S-phase kinase-associated protein 1

MacromoleculeName: S-phase kinase-associated protein 1 / type: protein_or_peptide / ID: 2 / Details: SKP1 fused Strep tag at the N-terminal / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 20.025492 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MWSHPQFEKG TMPTIKLQSS DGEIFEVDVE IAKQSVTIKT MLEDLGMDDE GDDDPVPLPN VNAAILKKVI QWCTHHKDDP PPPEDDENK EKRTDDIPVW DQEFLKVDQG TLFELILAAN YLDIKGLLDV TCKTVANMIK GKTPEEIRKT FNIKNDFTEE E EAQVRKEN QWCEEK

UniProtKB: S-phase kinase-associated protein 1

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Macromolecule #3: NACHT, LRR and PYD domains-containing protein 14

MacromoleculeName: NACHT, LRR and PYD domains-containing protein 14 / type: protein_or_peptide / ID: 3 / Details: NLRP14 fused Flag tag at the N-terminal / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 115.722227 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDKGD YKDDDDKGSM KTEDDEMEYE ASKEETVSED KDFDDGIDYR TVIKENIFTM WYKTSLHGEF ATLNCVITPK DQNLLQHIF DEDIQTSEAP QTVVLQGAAG IGKTTLLKKA VLEWADGNLY QQFTHVFYLN GKEISQVKEK SFAQLISKHW P SSEGPIEQ ...String:
DYKDDDDKGD YKDDDDKGSM KTEDDEMEYE ASKEETVSED KDFDDGIDYR TVIKENIFTM WYKTSLHGEF ATLNCVITPK DQNLLQHIF DEDIQTSEAP QTVVLQGAAG IGKTTLLKKA VLEWADGNLY QQFTHVFYLN GKEISQVKEK SFAQLISKHW P SSEGPIEQ VLSKPSSLLF IIDSFDELDF SFEEPQFALC KDWTQISPVS FLISSLLRKV MLPESYLLVA TRSTAWKRLV PL LQKPQRV KLSGLSKNAR MDYIHHLLKD KAWATSAIYS LRMNWRLFHM CHVCHMCQMI CAVLKGQVEK GGRVEETCKT STA LFTYYI CSLFPRIPVG CVTLPNETLL RSLCKAAVEG IWTMKHVLYQ QNLRKHELTR EDILLFLDAK VLQQDTEYEN CYMF THLHV QEFFAALFYL LRENLEEQDY PSEPFENLYL LLESNHIHDP HLEQMKCFLF GLLNKDRVRQ LEETFNLTIS MEVRE ELLA CLEGLEKDDS SLSQLRFQDL LHCIYETQDQ EFITQALMYF QKIIVRVDEE PQLRIYSFCL KHCHTLKTMR LTARAD LKN MLDTAEMCLE GAAVQVIHYW QDLFSVLHTN ESLIEMDLYE SRLDESLMKI LNEELSHPKC KLQKLIFRAV DFLNGCQ DF TFLASNKKVT HLDLKETDLG VNGLKTLCEA LKCKGCKLRV LRLASCDLNV ARCQKLSNAL QTNRSLVFLN LSLNNLSN D GVKSLCEVLE NPNSSLERLA LASCGLTKAG CKVLSSALTK SKRLTHLCLS DNVLEDEGIK LLSHTLKHPQ CTLQSLVLR SCSFTPIGSE HLSTALLHNR SLVHLDLGQN KLADNGVKLL CHSLQQPHCN LQELELMSCV LTSKACGDLA SVLVNNSNLW SLDLGHNIL DDAGLNILCD ALRNPNCHVQ RLGLENCGLT PGCCQDLLGI LSNNKSVIQM NLMKNALDHE SIKNLCKVLR S PTCKMEFL ALDKKEILKK KIKKFLVDVR INNPHLVIGP ECPNTESGCW WNYF

UniProtKB: NACHT, LRR and PYD domains-containing protein 14

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1.0 mg/mL
BufferpH: 8
VitrificationCryogen name: ETHANE / Chamber humidity: 100 %

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 53.633 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 105000
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.35 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 49652
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: PROJECTION MATCHING
FSC plot (resolution estimation)

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