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Structure paper

TitleAutoinhibition imposed by a large conformational switch of INO80 regulates nucleosome positioning.
Journal, issue, pagesScience, Vol. 389, Issue 6757, Page eadr3831, Year 2025
Publish dateJul 17, 2025
AuthorsUpneet Kaur / Hao Wu / Yifan Cheng / Geeta J Narlikar /
PubMed AbstractIncreasing the flanking DNA from 40 to 80 base pairs (bp) causes ~100-fold faster nucleosome sliding by INO80. A prevalent hypothesis posits that the Arp8 module within INO80 enables a ruler-like ...Increasing the flanking DNA from 40 to 80 base pairs (bp) causes ~100-fold faster nucleosome sliding by INO80. A prevalent hypothesis posits that the Arp8 module within INO80 enables a ruler-like activity. Using cryogenic electron microscopy, we show that on nucleosomes with 40 bp of flanking DNA, the Arp8 module rotates 180° away from the DNA. Deleting the Arp8 module enables rapid sliding irrespective of flanking DNA length. Thus, rather than enabling a ruler-like activity, the Arp8 module acts as a brake on INO80 remodeling when flanking DNA is short. This autoinhibition-based mechanism has broad implications for understanding how primitive nucleosome mobilization enzymes may have evolved into sophisticated remodelers.
External linksScience / PubMed:40674492 / PubMed Central
MethodsEM (single particle)
Resolution2.55 - 4.18 Å
Structure data

EMDB-45361, PDB-9c9g:
S.c INO80 in complex with S.c 0/80 nucleosome
Method: EM (single particle) / Resolution: 2.91 Å

EMDB-45369, PDB-9c9s:
S.c INO80 in complex with S.c 0/40 nucleosome, Class 1
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-45370, PDB-9c9t:
S.c INO80 in complex with S.c 0/40 nucleosome, Class 2
Method: EM (single particle) / Resolution: 3.16 Å

EMDB-45375, PDB-9c9x:
S.c INO80 in complex with Xenopus 0/80 nucleosome, Nucleosome
Method: EM (single particle) / Resolution: 2.83 Å

EMDB-45377, PDB-9c9z:
S.c INO80 in complex with Xenopus 0/80 nucleosome, INO80 Core
Method: EM (single particle) / Resolution: 2.55 Å

EMDB-45397, PDB-9can:
S.c INO80 in complex with Xenopus 0/40 nucleosome
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-45403, PDB-9cat:
DeltaArp8 INO80 bound to S.c 0/40 nucleosome, INO80 Core Module
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-45404, PDB-9cau:
DeltaArp8 INO80 bound to S.c 0/40 nucleosome, Nucleosome
Method: EM (single particle) / Resolution: 4.18 Å

EMDB-45418, PDB-9cb7:
DeltaNhp10 INO80 bound to S.c 0/40 nucleosome, Ino80-Nucleosome
Method: EM (single particle) / Resolution: 4.04 Å

EMDB-45441, PDB-9ccd:
DeltaNhp10 INO80 bound to S.c 0/40 nucleosome, INO80 core module
Method: EM (single particle) / Resolution: 3.01 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN/DNA / Chromatin Remodeler / nucleosome / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex

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