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TitleStructural basis of the subcortical maternal complex and its implications in reproductive disorders.
Journal, issue, pagesNat Struct Mol Biol, Vol. 31, Issue 1, Page 115-124, Year 2024
Publish dateJan 4, 2024
AuthorsPengliang Chi / Guojin Ou / Dandan Qin / Zhuo Han / Jialu Li / Qingjie Xiao / Zheng Gao / Chengpeng Xu / Qianqian Qi / Qingting Liu / Sibei Liu / Jinhong Li / Li Guo / Yuechao Lu / Jing Chen / Xiang Wang / Hubing Shi / Lei Li / Dong Deng /
PubMed AbstractThe subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly ...The subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly basis for SCMC remain elusive. Here we reconstituted mouse SCMC and solved the structure at atomic resolution using single-particle cryo-electron microscopy. The core complex of SCMC was formed by MATER, TLE6 and FLOPED, and MATER embraced TLE6 and FLOPED via its NACHT and LRR domains. Two core complexes further dimerize through interactions between two LRR domains of MATERs in vitro. FILIA integrates into SCMC by interacting with the carboxyl-terminal region of FLOPED. Zygotes from mice with Floped C-terminus truncation showed delayed development and resembled the phenotype of zygotes from Filia knockout mice. More importantly, the assembly of mouse SCMC was affected by corresponding clinical variants associated with female reproductive diseases and corresponded with a prediction based on the mouse SCMC structure. Our study paves the way for further investigations on SCMC functions during mammalian preimplantation embryonic development and reveals underlying causes of female reproductive diseases related to SCMC mutations, providing a new strategy for the diagnosis of female reproductive disorders.
External linksNat Struct Mol Biol / PubMed:38177687
MethodsEM (single particle)
Resolution2.78 - 3.38 Å
Structure data

34552

8h93

EMDB-34552, PDB-8h93:
Structure of dimeric mouse SCMC core complex
Method: EM (single particle) / Resolution: 3.01 Å

34554

8h94

EMDB-34554, PDB-8h94:
Structure of mouse SCMC bound with KH domain of FILIA
Method: EM (single particle) / Resolution: 2.9 Å

34555

8h95

EMDB-34555, PDB-8h95:
Structure of mouse SCMC bound with full-length FILIA
Method: EM (single particle) / Resolution: 3.38 Å

34556

8h96

EMDB-34556, PDB-8h96:
Structure of mouse SCMC core complex
Method: EM (single particle) / Resolution: 2.78 Å

Source
  • mus musculus (house mouse)
KeywordsCYTOSOLIC PROTEIN / oocyte / subcortical / complex

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