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TitleCryo-EM structure of ALC1 in an open conformation bound to a PARylated nucleosome.
Journal, issue, pagesActa Crystallogr D Struct Biol, Vol. 82, Issue Pt 6, Page 683-699, Year 2026
Publish dateJun 1, 2026
AuthorsHannah R Bridges / Luka Bacic / Sebastian Deindl / Guillaume Gaullier /
PubMed AbstractNucleosomes are the repeating unit of chromatin. They act as recognition platforms for chromatin-binding factors that coordinate genome maintenance. The chromatin remodeler Amplified in Liver Cancer ...Nucleosomes are the repeating unit of chromatin. They act as recognition platforms for chromatin-binding factors that coordinate genome maintenance. The chromatin remodeler Amplified in Liver Cancer 1 (ALC1) is a key component of the DNA-damage response and a promising therapeutic target in cancer. Through extensive classification of our previously deposited cryo-electron microscopy dataset, we identified a previously unresolved ALC1-nucleosome complex characterized by a more open conformation of ALC1. This is the first structure of ALC1 in which all domains are visualized in the context of a nucleosome complex, including the regulatory macro domain and a single α-helix motif within the linker. This newly identified conformation may represent an intermediate between the auto-inhibited and active states, and provides new structural insights into the conformational transitions that regulate the activity of ALC1.
External linksActa Crystallogr D Struct Biol / PubMed:42159202 / PubMed Central
MethodsEM (single particle)
Resolution2.96 - 6.6 Å
Structure data

55533

9t4v

EMDB-55533, PDB-9t4v:
ALC1/CHD1L in an intermediate conformation, bound to a PARylated nucleosome
Method: EM (single particle) / Resolution: 6.6 Å

EMDB-55534: Activation intermediate of ALC1/CHD1L bound to a PARylated nucleosome - regulatory linker segment resolved
Method: EM (single particle) / Resolution: 2.96 Å

Source
  • xenopus laevis (African clawed frog)
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / ALC1 / CHD1L / chromatin remodeler / DNA damage response / nucleosome / poly(ADP-ribose)

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