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TitleCryoDRGN-ET: deep reconstructing generative networks for visualizing dynamic biomolecules inside cells.
Journal, issue, pagesNat Methods, Year 2024
Publish dateJul 18, 2024
AuthorsRamya Rangan / Ryan Feathers / Sagar Khavnekar / Adam Lerer / Jake D Johnston / Ron Kelley / Martin Obr / Abhay Kotecha / Ellen D Zhong /
PubMed AbstractAdvances in cryo-electron tomography (cryo-ET) have produced new opportunities to visualize the structures of dynamic macromolecules in native cellular environments. While cryo-ET can reveal ...Advances in cryo-electron tomography (cryo-ET) have produced new opportunities to visualize the structures of dynamic macromolecules in native cellular environments. While cryo-ET can reveal structures at molecular resolution, image processing algorithms remain a bottleneck in resolving the heterogeneity of biomolecular structures in situ. Here, we introduce cryoDRGN-ET for heterogeneous reconstruction of cryo-ET subtomograms. CryoDRGN-ET learns a deep generative model of three-dimensional density maps directly from subtomogram tilt-series images and can capture states diverse in both composition and conformation. We validate this approach by recovering the known translational states in Mycoplasma pneumoniae ribosomes in situ. We then perform cryo-ET on cryogenic focused ion beam-milled Saccharomyces cerevisiae cells. CryoDRGN-ET reveals the structural landscape of S. cerevisiae ribosomes during translation and captures continuous motions of fatty acid synthase complexes inside cells. This method is openly available in the cryoDRGN software.
External linksNat Methods / PubMed:39025970
MethodsEM (subtomogram averaging)
Resolution4.5 - 8.8 Å
Structure data

EMDB-18231: CryoDRGN Reconstruction of 80S Ribosome in Rotated State from S.cerevisiae Prepared using Cryo-plasmaFIB Milling
Method: EM (subtomogram averaging) / Resolution: 4.7 Å

EMDB-18232: CryoDRGN Reconstruction of 80S Ribosome in Unrotated State from S.cerevisiae Prepared using Cryo-plasmaFIB Milling
Method: EM (subtomogram averaging) / Resolution: 4.5 Å

EMDB-45235: Subtomogram average (C1) of fatty acid synthase from S.cerevisiae prepared using cryo-plasmaFIB milling
Method: EM (subtomogram averaging) / Resolution: 8.8 Å

Source
  • Saccharomyces cerevisiae (brewer's yeast)

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