9LN6

Structure of human NLRP14-UHRF1 complex

Summary for 9LN6

• Entry DOI: 10.2210/pdb9ln6/pdb
• EMDB information: 63227
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,NACHT, LRR and PYD domains-containing protein 14, Maltose/maltodextrin-binding periplasmic protein,E3 ubiquitin-protein ligase UHRF1 (2 entities in total)
• Functional Keywords: maternal complex, uhrf1, nlrp14, ubiquitylation, cytosolic protein
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 2
• Total formula weight: 225512.50

Authors

Qi, Q.,Chi, P.,Liu, S.,Lu, Y.,Li, J.,Li, J.,Wang, X.,Jiang, Y.,Deng, D. (deposition date: 2025-01-20, release date: 2026-03-18, Last modification date: 2026-06-17)

Primary citation

Liu, S.,Qi, Q.,Chi, P.,Jiao, H.,Yan, L.,Lu, Y.,Zhang, R.,Li, J.,Ju, S.,Han, Z.,Zhang, Z.,Liu, Q.,Ou, G.,Li, J.,Chen, J.,Wang, X.,Li, L.,Guo, L.,Jiao, X.,Hu, H.,Jiang, Y.,Deng, D.
NLRP14 modulates the activity of E3 ubiquitin ligases during the oocyte-to-embryo transition.
Nat Commun, 17:-, 2026

PubMed 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 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.

PubMed: 41951593
DOI: 10.1038/s41467-026-71519-4

Experimental method

ELECTRON MICROSCOPY (3.49 Å)