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Title | Structural mechanism of extranucleosomal DNA readout by the INO80 complex. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 49, Page eadd3189, Year 2022 |
Publish date | Dec 9, 2022 |
Authors | Franziska Kunert / Felix J Metzner / James Jung / Markus Höpfler / Stephan Woike / Kevin Schall / Dirk Kostrewa / Manuela Moldt / Jia-Xuan Chen / Susanne Bantele / Boris Pfander / Sebastian Eustermann / Karl-Peter Hopfner / |
PubMed Abstract | The nucleosomal landscape of chromatin depends on the concerted action of chromatin remodelers. The INO80 remodeler specifically places nucleosomes at the boundary of gene regulatory elements, which ...The nucleosomal landscape of chromatin depends on the concerted action of chromatin remodelers. The INO80 remodeler specifically places nucleosomes at the boundary of gene regulatory elements, which is proposed to be the result of an ATP-dependent nucleosome sliding activity that is regulated by extranucleosomal DNA features. Here, we use cryo-electron microscopy and functional assays to reveal how INO80 binds and is regulated by extranucleosomal DNA. Structures of the regulatory A-module bound to DNA clarify the mechanism of linker DNA binding. The A-module is connected to the motor unit via an HSA/post-HSA lever element to chemomechanically couple the motor and linker DNA sensing. Two notable sites of curved DNA recognition by coordinated action of the four actin/actin-related proteins and the motor suggest how sliding by INO80 can be regulated by extranucleosomal DNA features. Last, the structures clarify the recruitment of YY1/Ies4 subunits and reveal deep architectural similarities between the regulatory modules of INO80 and SWI/SNF complexes. |
External links | Sci Adv / PubMed:36490333 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 - 7.7 Å |
Structure data | EMDB-15163: Cryo-EM reconstruction of Arp4-Ies4-N-actin-Arp8-Ino80HSA subcomplex (A-module) of INO80 EMDB-15164: Human Ino80 A-module + YY1 EMDB-15165, PDB-8a5d: EMDB-15177: Cryo-EM reconstruction of Arp4-Ies4-N-actin-Arp8-Ino80HSA subcomplex (A-module) of S. cerevisiae INO80 EMDB-15179: Cryo-EM reconstruction of Arp4-Ies4-N-actin-Arp8-Ino80HSA subcomplex (A-module) of S. cerevisiae INO80 EMDB-15180, PDB-8a5p: EMDB-15184, PDB-8a5q: EMDB-15186: Cryo-EM reconstruction of DNA bound Arp4-Ies4-N-actin-Arp8-Ino80HSA subcomplex (A-module) of S. cerevisiae INO80 EMDB-15187: A-module of Chaetomium thermophilum INO80 bound to curved DNA EMDB-15188: Nucleosome bound Chaetomium thermophilum INO80 (ADP-BeF3 state) core complex with Arp5 grappler in parallel conformation EMDB-15211: Ino80 core complex with A-module on nucleosome EMDB-15647, PDB-8atf: EMDB-15688: CryoEM structure of INO80 core nucleosome complex in closed grappler conformation (ADP-BeFx state) PDB-8av6: |
Chemicals | ChemComp-ATP: ChemComp-MG: ChemComp-AGS: ChemComp-ADP: |
Source |
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Keywords | DNA BINDING PROTEIN / chromatin remodeler / INO80 / Actin-related protein |