9L4K

Structure of human NLRP2-TLE6-OOEP complex

Summary for 9L4K

• Entry DOI: 10.2210/pdb9l4k/pdb
• EMDB information: 62814
• Descriptor: NACHT, LRR and PYD domains-containing protein 2, Transducin-like enhancer protein 6, Oocyte-expressed protein homolog (3 entities in total)
• Functional Keywords: complex, cytosolic protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 201402.04

Authors

Ou, G.J.,Liu, Q.T.,Jiao, H.Z.,Han, Z.,Li, J.H. (deposition date: 2024-12-20, release date: 2025-10-01, Last modification date: 2026-04-15)

Primary citation

Ou, G.,Liu, Q.,Jiao, H.,Han, Z.,Li, J.,Min, L.,Chi, P.,Liu, S.,Li, J.,Qi, Q.,Zhang, Z.,Guo, L.,Wang, X.,Li, L.,Chen, J.,Hu, H.,Deng, D.
Structural assembly of the subcortical maternal complex SCMC.
Structure, 34:20-31.e7, 2026

PubMed Abstract: The subcortical maternal complex (SCMC) is essential for mammalian preimplantation development, yet how SCMC (MATER/NLRP5, TLE6, FLOPED/OOEP) engages regulatory partners remains unclear. We determined cryo-EM structures of mouse SCMC bound to ZBED3 and human SCMC bound to NLRP2. Our structure reveals that ZBED3 interacts with all three SCMC subunits via its zinc finger domain, with conserved residue Phe73 mediating specific contacts. In contrast, human NLRP2 only binds to the WD40 domain of TLE6 through its leucine-rich repeat (LRR) domain. Similar interactions were also confirmed for NLRP7 with TLE6. These findings were cross-validated by in vivo proximity ligation and in vitro pull-down assays. Our work proposes a paradigmatic "Lego-like" assembly model, where the SCMC sequentially recruits different partners through diverse molecular interfaces. These findings provide critical structural insights into the SCMC's architecture and its multifaceted regulatory roles in early mammalian embryogenesis.

PubMed: 41118754
DOI: 10.1016/j.str.2025.09.009

Experimental method

ELECTRON MICROSCOPY (3.41 Å)