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A minority of final stacks yields superior amplitude in single-particle cryo-EM

Author

Listed:
  • Jianying Zhu

    (Tsinghua University)

  • Qi Zhang

    (Key Laboratory of Protein Sciences (Tsinghua University), Ministry of Education
    Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology
    Beijing Frontier Research Center for Biological Structure)

  • Hui Zhang

    (Tsinghua University)

  • Zuoqiang Shi

    (Tsinghua University
    Yanqi Lake Beijing Institute of Mathematical Sciences and Applications)

  • Mingxu Hu

    (Key Laboratory of Protein Sciences (Tsinghua University), Ministry of Education
    Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology
    Beijing Frontier Research Center for Biological Structure)

  • Chenglong Bao

    (Tsinghua University
    Yanqi Lake Beijing Institute of Mathematical Sciences and Applications
    Tsinghua University)

Abstract

Cryogenic electron microscopy (cryo-EM) is widely used to determine near-atomic resolution structures of biological macromolecules. Due to the low signal-to-noise ratio, cryo-EM relies on averaging many images. However, a crucial question in the field of cryo-EM remains unanswered: how close can we get to the minimum number of particles required to reach a specific resolution in practice? The absence of an answer to this question has impeded progress in understanding sample behavior and the performance of sample preparation methods. To address this issue, we develop an iterative particle sorting and/or sieving method called CryoSieve. Extensive experiments demonstrate that CryoSieve outperforms other cryo-EM particle sorting algorithms, revealing that most particles are unnecessary in final stacks. The minority of particles remaining in the final stacks yield superior high-resolution amplitude in reconstructed density maps. For some datasets, the size of the finest subset approaches the theoretical limit.

Suggested Citation

  • Jianying Zhu & Qi Zhang & Hui Zhang & Zuoqiang Shi & Mingxu Hu & Chenglong Bao, 2023. "A minority of final stacks yields superior amplitude in single-particle cryo-EM," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43555-x
    DOI: 10.1038/s41467-023-43555-x
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    References listed on IDEAS

    as
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