8H94

Structure of mouse SCMC bound with KH domain of FILIA

Summary for 8H94

• Entry DOI: 10.2210/pdb8h94/pdb
• EMDB information: 34554
• Descriptor: NACHT, LRR and PYD domains-containing protein 5, Transducin-like enhancer protein 6, Oocyte-expressed protein homolog (3 entities in total)
• Functional Keywords: oocyte, subcortical, complex, cytosolic protein
• Biological source: Mus musculus (Mouse,house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 203488.49

Authors

Chi, P.,Ou, G.,Han, Z.,Li, J.,Deng, D. (deposition date: 2022-10-24, release date: 2024-01-10, Last modification date: 2024-01-31)

Primary citation

Chi, P.,Ou, G.,Qin, D.,Han, Z.,Li, J.,Xiao, Q.,Gao, Z.,Xu, C.,Qi, Q.,Liu, Q.,Liu, S.,Li, J.,Guo, L.,Lu, Y.,Chen, J.,Wang, X.,Shi, H.,Li, L.,Deng, D.
Structural basis of the subcortical maternal complex and its implications in reproductive disorders.
Nat.Struct.Mol.Biol., 31:115-124, 2024

PubMed Abstract: 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.

PubMed: 38177687
DOI: 10.1038/s41594-023-01153-x

Experimental method

ELECTRON MICROSCOPY (2.9 Å)