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Structural assembly of the subcortical maternal complex SCMC.

Guojin Ou1, Qingting Liu1, Haizhan Jiao2

  • 1Department of Laboratory Medicine, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu 610041, China; Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Sichuan University, Chengdu 610041, China.

Structure (London, England : 1993)
|October 21, 2025
PubMed
Summary

The subcortical maternal complex (SCMC) core structure was revealed, showing how it binds regulatory partners like ZBED3 and NLRP2. This provides key insights into early mammalian embryo development.

Keywords:
Lego-like assembly modelcryo-EMearly mammalian embryogenesispathogenic variantssubcortical maternal complex

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Area of Science:

  • Structural Biology
  • Developmental Biology
  • Genetics

Background:

  • The subcortical maternal complex (SCMC) is crucial for mammalian preimplantation development.
  • Understanding how the SCMC core interacts with regulatory partners is essential but remains unclear.

Purpose of the Study:

  • To determine the cryo-electron microscopy (cryo-EM) structures of mouse and human SCMC bound to regulatory partners.
  • To elucidate the molecular mechanisms underlying SCMC complex assembly and its interactions with ZBED3, NLRP2, and NLRP7.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
  • In vivo proximity ligation assays and in vitro pull-down assays for cross-validation.

Main Results:

  • Determined structures of mouse SCMC with ZBED3 and human SCMC with NLRP2.
  • ZBED3 interacts with all SCMC core subunits (MATER/NLRP5, TLE6, FLOPED/OOEP) via its zinc finger domain.
  • NLRP2 and NLRP7 bind to TLE6 through specific domain interactions (LRR and WD40 domains).

Conclusions:

  • Proposes a 'Lego-like' assembly model for SCMC complex formation.
  • Highlights diverse molecular interfaces for SCMC core recruitment of regulatory partners.
  • Provides critical structural insights into SCMC architecture and its roles in early mammalian embryogenesis.