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-Structure paper
| Title | Autoinhibition imposed by a large conformational switch of INO80 regulates nucleosome positioning. |
|---|---|
| Journal, issue, pages | Science, Vol. 389, Issue 6757, Page eadr3831, Year 2025 |
| Publish date | Jul 17, 2025 |
Authors | Upneet Kaur / Hao Wu / Yifan Cheng / Geeta J Narlikar / ![]() |
| PubMed Abstract | 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 ...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 links | Science / PubMed:40674492 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.55 - 4.18 Å |
| Structure data | EMDB-45361, PDB-9c9g: EMDB-45369, PDB-9c9s: EMDB-45370, PDB-9c9t: EMDB-45375, PDB-9c9x: EMDB-45377, PDB-9c9z: EMDB-45397, PDB-9can: EMDB-45403, PDB-9cat: EMDB-45404, PDB-9cau: EMDB-45418, PDB-9cb7: EMDB-45441, PDB-9ccd: |
| Chemicals | ![]() ChemComp-ADP: |
| Source |
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Keywords | DNA BINDING PROTEIN/DNA / Chromatin Remodeler / nucleosome / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex |
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