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TitleCryo-EM structure of the human subcortical maternal complex and the associated discovery of infertility-associated variants.
Journal, issue, pagesNat Struct Mol Biol, Year 2024
Publish dateOct 8, 2024
AuthorsPengliang Chi / Guojin Ou / Sibei Liu / Qianhong Ma / Yuechao Lu / Jinhong Li / Jialu Li / Qianqian Qi / Zhuo Han / Zihan Zhang / Qingting Liu / Li Guo / Jing Chen / Xiang Wang / Wei Huang / Lei Li / Dong Deng /
PubMed AbstractThe functionally conserved subcortical maternal complex (SCMC) is essential for early embryonic development in mammals. Reproductive disorders caused by pathogenic variants in NLRP5, TLE6 and OOEP, ...The functionally conserved subcortical maternal complex (SCMC) is essential for early embryonic development in mammals. Reproductive disorders caused by pathogenic variants in NLRP5, TLE6 and OOEP, three core components of the SCMC, have attracted much attention over the past several years. Evaluating the pathogenicity of a missense variant in the SCMC is limited by the lack of information on its structure, although we recently solved the structure of the mouse SCMC and proposed that reproductive disorders caused by pathogenic variants are related to the destabilization of the SCMC core complex. Here we report the cryogenic electron microscopy structure of the human SCMC and uncover that the pyrin domain of NLRP5 is essential for the stability of SCMC. By combining prediction of SCMC stability and in vitro reconstitution, we provide a method for identifying deleterious variants, and we successfully identify a new pathogenic variant of TLE6 (p.A396T). Thus, on the basis of the structure of the human SCMC, we offer a strategy for the diagnosis of reproductive disorders and the discovery of new infertility-associated variants.
External linksNat Struct Mol Biol / PubMed:39379527
MethodsEM (single particle)
Resolution3.01 - 3.36 Å
Structure data

38128

8x7v

EMDB-38128, PDB-8x7v:
Structure of human SCMC ternary complex
Method: EM (single particle) / Resolution: 3.01 Å

38129

8x7w

EMDB-38129, PDB-8x7w:
Structure of dimeric human SCMC complex
Method: EM (single particle) / Resolution: 3.36 Å

Source
  • homo sapiens (human)
  • escherichia coli k-12 (bacteria)
KeywordsCYTOSOLIC PROTEIN / oocyte / subcortical / complex

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