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TitleMechanisms of chromatin remodeling by an Snf2-type ATPase.
Journal, issue, pagesbioRxiv, Year 2025
Publish dateJan 2, 2025
AuthorsDeepshikha Malik / Ashish Deshmukh / Silvija Bilokapic / Mario Halic /
PubMed AbstractChromatin remodeling enzymes play a crucial role in the organization of chromatin, enabling both stability and plasticity of genome regulation. These enzymes use a Snf2-type ATPase motor to move ...Chromatin remodeling enzymes play a crucial role in the organization of chromatin, enabling both stability and plasticity of genome regulation. These enzymes use a Snf2-type ATPase motor to move nucleosomes, but how they translocate DNA around the histone octamer is unclear. Here we use cryo-EM to visualize the continuous motion of nucleosomal DNA induced by human chromatin remodeler SNF2H, an ISWI family member. Our work reveals conformational changes in SNF2H, DNA and histones during nucleosome sliding and provides the structural basis for DNA translocation. ATP hydrolysis induces conformational changes in SNF2H that pull the DNA tracking strand, distorting DNA and histones at SHL2. This is followed by SNF2H rotation on the nucleosome, which first pulls the DNA guide strand and creates one-base pair bulge at SHL2, and then releases the pulled DNA. Given the high conservation of the catalytic motors among ATP-dependent chromatin remodelers, the mechanisms we describe likely apply to other families.
External linksbioRxiv / PubMed:39803580 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 4.2 Å
Structure data

47421

9e1u

EMDB-47421, PDB-9e1u:
Snf2h bound nucleosome complex - ClassC1
Method: EM (single particle) / Resolution: 3.1 Å

47424

9e1x

EMDB-47424, PDB-9e1x:
Snf2h bound nucleosome complex - ClassD1
Method: EM (single particle) / Resolution: 3.4 Å

47425

9e1y

EMDB-47425, PDB-9e1y:
Empty Nucleosome with 601 widom sequence
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-47427: SNF2H bound to nucleosome - Class E1
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-47428: SNF2H bound to nucleosome - Class E2
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

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

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN/DNA / chromatin remodeling / remodelers / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex / SNF2H; chromatin remodeling / ISWI / nucleosome / Chromatin

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