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- PDB-8ifg: Cryo-EM structure of the Clr6S (Clr6-HDAC) complex from S. pombe -

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Basic information

Entry
Database: PDB / ID: 8ifg
TitleCryo-EM structure of the Clr6S (Clr6-HDAC) complex from S. pombe
Components
  • Chromatin modification-related protein eaf3
  • Cph1
  • Cph2
  • Histone deacetylase clr6
  • Paired amphipathic helix protein pst2
  • RbAp48-related WD40 repeat-containing protein prw1
KeywordsTRANSCRIPTION / Rpd3S / Histone deacetylase / HDAC / Clr6 / Rpd3 / Clr6S / Clr6 HDAC
Function / homology
Function and homology information


histone H4K16 deacetylase activity, hydrolytic mechanism / histone H4K5 deacetylase activity, hydrolytic mechanism / histone H4K8 deacetylase activity, hydrolytic mechanism / histone H3K9 deacetylase activity, hydrolytic mechanism / histone H3K14 deacetylase activity, hydrolytic mechanism / HDACs deacetylate histones / histone H4K12 deacetylase activity, hydrolytic mechanism / SUMOylation of chromatin organization proteins / H3-H4 histone complex chaperone activity / Rpd3L complex ...histone H4K16 deacetylase activity, hydrolytic mechanism / histone H4K5 deacetylase activity, hydrolytic mechanism / histone H4K8 deacetylase activity, hydrolytic mechanism / histone H3K9 deacetylase activity, hydrolytic mechanism / histone H3K14 deacetylase activity, hydrolytic mechanism / HDACs deacetylate histones / histone H4K12 deacetylase activity, hydrolytic mechanism / SUMOylation of chromatin organization proteins / H3-H4 histone complex chaperone activity / Rpd3L complex / Rpd3L-Expanded complex / Rpd3S complex / histone deacetylase / protein lysine deacetylase activity / DNA repair-dependent chromatin remodeling / histone deacetylase activity / NuA4 histone acetyltransferase complex / Sin3-type complex / epigenetic regulation of gene expression / transcription initiation-coupled chromatin remodeling / heterochromatin formation / mitotic spindle / transcription corepressor activity / histone binding / molecular adaptor activity / chromatin remodeling / DNA repair / regulation of DNA-templated transcription / chromatin / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / nucleus / metal ion binding / cytosol / cytoplasm
Similarity search - Function
: / : / MSL3 chromodomain-like / Histone deacetylase interacting domain / Sin3, C-terminal / Transcriptional regulatory protein Sin3-like / Sin3 family co-repressor / C-terminal domain of Sin3a protein / Histone deacetylase (HDAC) interacting / Paired amphipathic helix ...: / : / MSL3 chromodomain-like / Histone deacetylase interacting domain / Sin3, C-terminal / Transcriptional regulatory protein Sin3-like / Sin3 family co-repressor / C-terminal domain of Sin3a protein / Histone deacetylase (HDAC) interacting / Paired amphipathic helix / Paired amphipathic helix superfamily / Paired amphipathic helix repeat / PAH domain profile. / MRG / MRG domain / MRG, C-terminal domain superfamily / MRG / MRG domain profile. / Histone-binding protein RBBP4, N-terminal / : / Histone-binding protein RBBP4 or subunit C of CAF1 complex / Histone deacetylase / Chromo/chromo shadow domain / Chromatin organization modifier domain / : / Chromo-like domain superfamily / Histone deacetylase family / Histone deacetylase domain / Histone deacetylase domain superfamily / Histone deacetylase domain / Ureohydrolase domain superfamily / Zinc finger, PHD-type, conserved site / PHD-finger / Zinc finger PHD-type signature. / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Zinc finger, PHD-type / PHD zinc finger / Zinc finger, FYVE/PHD-type / G-protein beta WD-40 repeat / Zinc finger, RING/FYVE/PHD-type / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Paired amphipathic helix protein pst2 / Chromatin modification-related protein eaf3 / RbAp48-related WD40 repeat-containing protein prw1 / Histone deacetylase clr6 / Uncharacterized protein C2F7.07c / Uncharacterized protein C16C9.05
Similarity search - Component
Biological speciesSchizosaccharomyces pombe (fission yeast)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsZhang, H.Q. / Wang, X. / Wang, Y.N. / Liu, S.M. / Zhang, Y. / Xu, K. / Ji, L.T. / Kornberg, R.D.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Proc Natl Acad Sci U S A / Year: 2023
Title: Class I histone deacetylase complex: Structure and functional correlates.
Authors: Xiao Wang / Yannan Wang / Simiao Liu / Yi Zhang / Ke Xu / Liting Ji / Roger D Kornberg / Heqiao Zhang /
Abstract: The Clr6S complex, a class I histone deacetylase complex, functions as a zinc-dependent enzyme to remove acetyl groups from lysine residues in histone tails. We report here the cryo-EM structure of ...The Clr6S complex, a class I histone deacetylase complex, functions as a zinc-dependent enzyme to remove acetyl groups from lysine residues in histone tails. We report here the cryo-EM structure of Clr6S alone and a cryo-EM map of Clr6S in complex with a nucleosome. The active center, revealed at near-atomic resolution, includes features important for catalysis-A water molecule coordinated by zinc, the likely nucleophile for attack on the acetyl-lysine bond, and a loop that may position the substrate for catalysis. The cryo-EM map in the presence of a nucleosome reveals multiple Clr6S-nucleosome contacts and a high degree of relative motion of Clr6S and the nucleosome. Such flexibility may be attributed to interaction at a site in the flexible histone tail and is likely important for the function of the deacetylase, which acts at multiple sites in other histone tails.
History
DepositionFeb 17, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jan 3, 2024Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
B: RbAp48-related WD40 repeat-containing protein prw1
A: Paired amphipathic helix protein pst2
C: Histone deacetylase clr6
E: Chromatin modification-related protein eaf3
D: Chromatin modification-related protein eaf3
F: Cph1
P: Cph2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)411,81010
Polymers411,6147
Non-polymers1963
Water181
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 6 types, 7 molecules BACEDFP

#1: Protein RbAp48-related WD40 repeat-containing protein prw1


Mass: 48528.926 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Schizosaccharomyces pombe (strain 972 / ATCC 24843) (yeast)
Gene: prw1, SPAC29A4.18 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: O14021
#2: Protein Paired amphipathic helix protein pst2 / SIN3 homolog 2


Mass: 125011.609 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Schizosaccharomyces pombe (strain 972 / ATCC 24843) (yeast)
Gene: pst2, SPAC23C11.15 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: O13919
#3: Protein Histone deacetylase clr6 / Cryptic loci regulator 6


Mass: 45773.371 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Schizosaccharomyces pombe (strain 972 / ATCC 24843) (yeast)
Gene: clr6, SPBC36.05c / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: O59702, histone deacetylase
#4: Protein Chromatin modification-related protein eaf3 / Altered polarity protein 13 / ESA1-associated factor 3


Mass: 39191.199 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Schizosaccharomyces pombe (strain 972 / ATCC 24843) (yeast)
Gene: alp13, eaf3, SPAC23H4.12 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: O13953
#5: Protein Cph1


Mass: 45046.082 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Schizosaccharomyces pombe (strain 972 / ATCC 24843) (yeast)
Gene: SPAC16C9.05 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q09819
#6: Protein Cph2


Mass: 68871.703 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Schizosaccharomyces pombe (strain 972 / ATCC 24843) (yeast)
Gene: SPAC2F7.07c / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q09698

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Non-polymers , 2 types, 4 molecules

#7: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Cryo-EM structure of the Clr6-HDAC (Clr6S) complex from S. pombe
Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT
Molecular weightValue: 0.6 MDa / Experimental value: YES
Source (natural)Organism: Schizosaccharomyces pombe (fission yeast)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 721645 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.01219542
ELECTRON MICROSCOPYf_angle_d0.71326495
ELECTRON MICROSCOPYf_dihedral_angle_d11.5682557
ELECTRON MICROSCOPYf_chiral_restr0.0462873
ELECTRON MICROSCOPYf_plane_restr0.0063416

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