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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhou, B-R; Yadav, KNS; Borgnia, M; Hong, J; Cao, B; Olins, AL; Olins, DE; Bai, Y; Zhang, P

Published Date

  • May 24, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 2301 -

PubMed ID

  • 31127102

Pubmed Central ID

  • 31127102

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-10247-4

Language

  • eng

Conference Location

  • England