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Atomic resolution cryo-EM structure of a native-like CENP-A nucleosome aided by an antibody fragment

Author

Listed:
  • Bing-Rui Zhou

    (National Institutes of Health)

  • K. N. Sathish Yadav

    (National Institutes of Health)

  • Mario Borgnia

    (National Institutes of Health)

  • Jingjun Hong

    (National Institutes of Health)

  • Baohua Cao

    (National Institutes of Health)

  • Ada L. Olins

    (University of New England)

  • Donald E. Olins

    (University of New England)

  • Yawen Bai

    (National Institutes of Health)

  • Ping Zhang

    (National Institutes of Health)

Abstract

Genomic DNA in eukaryotes is organized into chromatin through association with core histones to form nucleosomes, each distinguished by their DNA sequences and histone variants. Here, we used a single-chain antibody fragment (scFv) derived from the anti-nucleosome antibody mAb PL2-6 to stabilize human CENP-A nucleosome containing a native α-satellite DNA and solved its structure by the cryo-electron microscopy (cryo-EM) to 2.6 Å resolution. In comparison, the corresponding cryo-EM structure of the free CENP-A nucleosome could only reach 3.4 Å resolution. We find that scFv binds to a conserved acidic patch on the histone H2A-H2B dimer without perturbing the nucleosome structure. Our results provide an atomic resolution cryo-EM structure of a nucleosome and insight into the structure and function of the CENP-A nucleosome. The scFv approach is applicable to the structural determination of other native-like nucleosomes with distinct DNA sequences.

Suggested Citation

  • Bing-Rui Zhou & K. N. Sathish Yadav & Mario Borgnia & Jingjun Hong & Baohua Cao & Ada L. Olins & Donald E. Olins & Yawen Bai & Ping Zhang, 2019. "Atomic resolution cryo-EM structure of a native-like CENP-A nucleosome aided by an antibody fragment," Nature Communications, Nature, vol. 10(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10247-4
    DOI: 10.1038/s41467-019-10247-4
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    Cited by:

    1. Harsh Nagpal & Ahmad Ali-Ahmad & Yasuhiro Hirano & Wei Cai & Mario Halic & Tatsuo Fukagawa & Nikolina Sekulić & Beat Fierz, 2023. "CENP-A and CENP-B collaborate to create an open centromeric chromatin state," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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