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Structure paper

TitleMolecular basis of global promoter sensing and nucleosome capture by the SWR1 chromatin remodeler.
Journal, issue, pagesCell, Year 2024
Publish dateSep 27, 2024
AuthorsRobert K Louder / Giho Park / Ziyang Ye / Justin S Cha / Anne M Gardner / Qin Lei / Anand Ranjan / Eva Höllmüller / Florian Stengel / B Franklin Pugh / Carl Wu /
PubMed AbstractThe SWR1 chromatin remodeling complex is recruited to +1 nucleosomes downstream of transcription start sites of eukaryotic promoters, where it exchanges histone H2A for the specialized variant H2A.Z. ...The SWR1 chromatin remodeling complex is recruited to +1 nucleosomes downstream of transcription start sites of eukaryotic promoters, where it exchanges histone H2A for the specialized variant H2A.Z. Here, we use cryoelectron microscopy (cryo-EM) to resolve the structural basis of the SWR1 interaction with free DNA, revealing a distinct open conformation of the Swr1 ATPase that enables sliding from accessible DNA to nucleosomes. A complete structural model of the SWR1-nucleosome complex illustrates critical roles for Swc2 and Swc3 subunits in oriented nucleosome engagement by SWR1. Moreover, an extended DNA-binding α helix within the Swc3 subunit enables sensing of nucleosome linker length and is essential for SWR1-promoter-specific recruitment and activity. The previously unresolved N-SWR1 subcomplex forms a flexible extended structure, enabling multivalent recognition of acetylated histone tails by reader domains to further direct SWR1 toward the +1 nucleosome. Altogether, our findings provide a generalizable mechanism for promoter-specific targeting of chromatin and transcription complexes.
External linksCell / PubMed:39357520
MethodsEM (single particle)
Resolution3.3 - 7.3 Å
Structure data

44074

9b1d

EMDB-44074, PDB-9b1d:
Cryo-EM structure of native SWR1 bound to DNA (composite structure)
Method: EM (single particle) / Resolution: 3.3 Å

44075

9b1e

EMDB-44075, PDB-9b1e:
Cryo-EM structure of native SWR1 bound to nucleosome (composite structure)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-44093: Cryo-EM structure of native SWR1, free complex (composite structure)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-44106: Cryo-EM structure of native SWR1 bound to DNA (consensus map)
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-44107: RuvBL core from SWR1-DNA complex (focused refinement)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-44108: Swr1 ATPase domain from SWR1-DNA complex (focused refinement)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-44109: Arp6/Swc6 module from SWR1-DNA complex (focused refinement)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-44110: Cryo-EM structure of native SWR1 bound to DNA (unmasked refinement filtered by local resolution)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-44307: Cryo-EM structure of native SWR1 bound to nucleosome (consensus map filtered by local resolution)
Method: EM (single particle) / Resolution: 6.2 Å

EMDB-44308: RuvBL-associated core from SWR1-nucleosome complex (focused refinement)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-44309: Nucleosome and bound Swr1 ATPase from SWR1-nucleosome complex (focused refinement)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-44310: Swc3-Swc2 subcomplex from SWR1-nucleosome complex (focused refinement)
Method: EM (single particle) / Resolution: 7.3 Å

EMDB-44311: Cryo-EM structure of native SWR1, free complex (consensus map filtered by local resolution)
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-44312: RuvBL core from free SWR1 complex (focused refinement)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-44313: Arp6/Swc6 module from free SWR1 complex (focused refinement)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-46065: Cryo-EM structure of native SWR1 bound to DNA in the absence of nucleotide (composite structure)
Method: EM (single particle) / Resolution: 5.8 Å

EMDB-46066: Cryo-EM structure of native SWR1 bound to DNA in the absence of nucleotide (consensus map)
Method: EM (single particle) / Resolution: 5.8 Å

EMDB-46067: RuvBL core from SWR1(apo)-DNA complex (focused refinement)
Method: EM (single particle) / Resolution: 5.5 Å

EMDB-46068: Arp6/Swc6 module from SWR1(apo)-DNA complex (focused refinement)
Method: EM (single particle) / Resolution: 7.2 Å

EMDB-46069: Swr1 ATPase domain from SWR1(apo)-DNA complex (focused refinement)
Method: EM (single particle) / Resolution: 7.1 Å

Chemicals

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

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

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • saccharomyces cerevisiae w303 (yeast)
  • synthetic construct (others)
  • drosophila melanogaster (fruit fly)
KeywordsGENE REGULATION / Chromatin Remodeler / Snf2 family ATPase / histone exchange / H2A.Z

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