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TitleStructural assembly of the subcortical maternal complex SCMC.
Journal, issue, pagesStructure, Vol. 34, Issue 1, Page 20-31.e7, Year 2026
Publish dateJan 8, 2026
AuthorsGuojin Ou / Qingting Liu / Haizhan Jiao / Zhuo Han / Jinhong Li / Ling Min / Pengliang Chi / Sibei Liu / Jialu Li / Qianqian Qi / Zihan Zhang / Li Guo / Xiang Wang / Lei Li / Jing Chen / Hongli Hu / Dong Deng /
PubMed AbstractThe subcortical maternal complex (SCMC) is essential for mammalian preimplantation development, yet how SCMC (MATER/NLRP5, TLE6, FLOPED/OOEP) engages regulatory partners remains unclear. We ...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.
External linksStructure / PubMed:41118754
MethodsEM (single particle)
Resolution3.0 - 3.41 Å
Structure data

62813

9l4j

EMDB-62813, PDB-9l4j:
Structure of mouse SCMCcore complex contain ZBED3
Method: EM (single particle) / Resolution: 3.0 Å

62814

9l4k

EMDB-62814, PDB-9l4k:
Structure of human NLRP2-TLE6-OOEP complex
Method: EM (single particle) / Resolution: 3.41 Å

62815

9l4l

EMDB-62815, PDB-9l4l:
Structure of human SCMCcore complex contain NLRP2
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • mus musculus (house mouse)
  • homo sapiens (human)
KeywordsCYTOSOLIC PROTEIN / complex

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