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TitleHexasome-INO80 complex reveals structural basis of noncanonical nucleosome remodeling.
Journal, issue, pagesScience, Vol. 381, Issue 6655, Page 313-319, Year 2023
Publish dateJul 21, 2023
AuthorsMin Zhang / Anna Jungblut / Franziska Kunert / Luis Hauptmann / Thomas Hoffmann / Olga Kolesnikova / Felix Metzner / Manuela Moldt / Felix Weis / Frank DiMaio / Karl-Peter Hopfner / Sebastian Eustermann /
PubMed AbstractLoss of H2A-H2B histone dimers is a hallmark of actively transcribed genes, but how the cellular machinery functions in the context of noncanonical nucleosomal particles remains largely elusive. In ...Loss of H2A-H2B histone dimers is a hallmark of actively transcribed genes, but how the cellular machinery functions in the context of noncanonical nucleosomal particles remains largely elusive. In this work, we report the structural mechanism for adenosine 5'-triphosphate-dependent chromatin remodeling of hexasomes by the INO80 complex. We show how INO80 recognizes noncanonical DNA and histone features of hexasomes that emerge from the loss of H2A-H2B. A large structural rearrangement switches the catalytic core of INO80 into a distinct, spin-rotated mode of remodeling while its nuclear actin module remains tethered to long stretches of unwrapped linker DNA. Direct sensing of an exposed H3-H4 histone interface activates INO80, independently of the H2A-H2B acidic patch. Our findings reveal how the loss of H2A-H2B grants remodelers access to a different, yet unexplored layer of energy-driven chromatin regulation.
External linksScience / PubMed:37384673
MethodsEM (single particle)
Resolution2.7 - 7.59 Å
Structure data

17006

8oo7

EMDB-17006: CryoEM Structure INO80core Hexasome complex composite map state1
PDB-8oo7: CryoEM Structure INO80core Hexasome complex composite model state1
Method: EM (single particle) / Resolution: 2.8 Å

17007

8oo9

EMDB-17007, PDB-8oo9:
CryoEM Structure INO80core Hexasome complex ATPase-DNA refinement state1
Method: EM (single particle) / Resolution: 3.2 Å

17008

8ooa

EMDB-17008, PDB-8ooa:
CryoEM Structure INO80core Hexasome complex Hexasome refinement state1
Method: EM (single particle) / Resolution: 3.18 Å

17010

8ooc

EMDB-17010, PDB-8ooc:
CryoEM Structure INO80core Hexasome complex Rvb core refinement state1
Method: EM (single particle) / Resolution: 2.93 Å

17012

8oof

EMDB-17012, PDB-8oof:
CryoEM Structure INO80core Hexasome complex Arp5 Ies6 refinement state1
Method: EM (single particle) / Resolution: 2.9 Å

17017

8ook

EMDB-17017, PDB-8ook:
CryoEM Structure INO80core Hexasome complex Arp5 grappler refinement state1
Method: EM (single particle) / Resolution: 5.69 Å

17025

8oop

EMDB-17025: INO80 core bound to hexasome composite map of state 2
PDB-8oop: CryoEM Structure INO80core Hexasome complex composite model state2
Method: EM (single particle) / Resolution: 2.7 Å

17026

8oor

EMDB-17026, PDB-8oor:
CryoEM Structure INO80core Hexasome complex Rvb core refinement state2
Method: EM (single particle) / Resolution: 2.87 Å

17027

8oos

EMDB-17027, PDB-8oos:
CryoEM Structure INO80core Hexasome complex ATPase-hexasome refinement state 2
Method: EM (single particle) / Resolution: 3.29 Å

17028

8oot

EMDB-17028, PDB-8oot:
CryoEM Structure INO80core Hexasome complex Arp5 Ies6 refinement state2
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-17676: INO80 core bound to hexasome focused refinement of Arp5 grappler
Method: EM (single particle) / Resolution: 7.59 Å

Chemicals

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

ChemComp-ALF:
TETRAFLUOROALUMINATE ION

ChemComp-MG:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

Source
  • thermochaetoides thermophila (fungus)
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / ATP-dependent chromatin remodeler

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