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- PDB-9y3d: Extended cryo-EM structure of the human SRCAP-nucleosome complex ... -

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Entry
Database: PDB / ID: 9y3d
TitleExtended cryo-EM structure of the human SRCAP-nucleosome complex in the fully-engaged state, with H4-bound GAS41
Components
  • (DNA (285-MER)) x 2
  • Actin, cytoplasmic 1
  • Actin-like protein 6A
  • Actin-related protein 6
  • DNA methyltransferase 1-associated protein 1
  • Helicase SRCAP
  • Histone H2A type 1
  • Histone H2B 1.1
  • Histone H3.2
  • Histone H4
  • RuvB-like 1
  • RuvB-like 2
  • Vacuolar protein sorting-associated protein 72 homolog
  • YEATS domain-containing protein 4
  • Zinc finger HIT domain-containing protein 1
KeywordsGENE REGULATION / HYDROLASE/DNA BINDING PROTEIN/DNA / Chromatin Remodeler / Snf2 family ATPase / H2A.Z / HYDROLASE-DNA BINDING PROTEIN-DNA complex
Function / homology
Function and homology information


positive regulation of lymphoid progenitor cell differentiation / histone H3K18ac reader activity / catalytic activity, acting on a protein / hematopoietic stem cell homeostasis / intestinal stem cell homeostasis / RPAP3/R2TP/prefoldin-like complex / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / npBAF complex / positive regulation of norepinephrine uptake ...positive regulation of lymphoid progenitor cell differentiation / histone H3K18ac reader activity / catalytic activity, acting on a protein / hematopoietic stem cell homeostasis / intestinal stem cell homeostasis / RPAP3/R2TP/prefoldin-like complex / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / npBAF complex / positive regulation of norepinephrine uptake / muscle cell differentiation / positive regulation of telomere maintenance in response to DNA damage / regulation of DNA strand elongation / histone chaperone activity / R2TP complex / dynein axonemal particle / cellular response to cytochalasin B / neural retina development / Formation of the embryonic stem cell BAF (esBAF) complex / regulation of transepithelial transport / Activation of the TFAP2 (AP-2) family of transcription factors / Formation of the canonical BAF (cBAF) complex / morphogenesis of a polarized epithelium / Formation of annular gap junctions / Formation of the dystrophin-glycoprotein complex (DGC) / structural constituent of postsynaptic actin cytoskeleton / Swr1 complex / Formation of the polybromo-BAF (pBAF) complex / Gap junction degradation / GBP-mediated host defense / protein localization to adherens junction / Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) / establishment of protein localization to chromatin / Formation of the non-canonical BAF (ncBAF) complex / Cell-extracellular matrix interactions / heart process / regulation of G0 to G1 transition / dense body / Folding of actin by CCT/TriC / Tat protein binding / postsynaptic actin cytoskeleton / Ino80 complex / Regulation of CDH1 Function / apical protein localization / negative regulation of transcription by RNA polymerase I / Prefoldin mediated transfer of substrate to CCT/TriC / Adherens junctions interactions / regulation of double-strand break repair / microtubule nucleation / SWI/SNF complex / adherens junction assembly / RHOF GTPase cycle / box C/D snoRNP assembly / Sensory processing of sound by outer hair cells of the cochlea / ATP-dependent chromatin remodeler activity / tight junction / Sensory processing of sound by inner hair cells of the cochlea / nucleolus organization / regulation of mitotic metaphase/anaphase transition / positive regulation of DNA damage response, signal transduction by p53 class mediator / spinal cord development / positive regulation of T cell differentiation / maintenance of blood-brain barrier / Interaction between L1 and Ankyrins / apical junction complex / regulation of nucleotide-excision repair / positive regulation of stem cell population maintenance / regulation of chromosome organization / positive regulation of transcription by RNA polymerase I / NuA4 histone acetyltransferase complex / regulation of norepinephrine uptake / transporter regulator activity / histone H3K27ac reader activity / Recycling pathway of L1 / cortical cytoskeleton / positive regulation of double-strand break repair / MLL1 complex / Regulation of MITF-M-dependent genes involved in pigmentation / negative regulation of cell differentiation / establishment or maintenance of cell polarity / regulation of DNA replication / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / nitric-oxide synthase binding / TFIID-class transcription factor complex binding / brush border / EPH-ephrin mediated repulsion of cells / protein folding chaperone complex / Telomere Extension By Telomerase / positive regulation of transcription initiation by RNA polymerase II / regulation of synaptic vesicle endocytosis / positive regulation of myoblast differentiation / RHO GTPases Activate WASPs and WAVEs / cAMP/PKA signal transduction / kinesin binding / RNA polymerase II core promoter sequence-specific DNA binding / calcium ion homeostasis / regulation of protein localization to plasma membrane / RHO GTPases activate IQGAPs / positive regulation of double-strand break repair via homologous recombination / nucleosome binding
Similarity search - Function
DNA methyltransferase 1-associated 1 / DNA methyltransferase 1-associated protein 1 (DMAP1) / SWR1-complex protein 4/DNA methyltransferase 1-associated protein 1 / DAMP1, SANT/Myb-like domain / SANT/Myb-like domain of DAMP1 / YEATS / Vps71/ZNHIT1 / HIT zinc finger / Zinc finger HIT-type profile. / Vps72/YL1, N-terminal ...DNA methyltransferase 1-associated 1 / DNA methyltransferase 1-associated protein 1 (DMAP1) / SWR1-complex protein 4/DNA methyltransferase 1-associated protein 1 / DAMP1, SANT/Myb-like domain / SANT/Myb-like domain of DAMP1 / YEATS / Vps71/ZNHIT1 / HIT zinc finger / Zinc finger HIT-type profile. / Vps72/YL1, N-terminal / YL1 nuclear protein / Zinc finger, HIT-type / : / : / YEATS superfamily / YEATS family / YEATS domain profile. / Vps72/YL1, C-terminal / YL1 nuclear protein C-terminal domain / YL1 nuclear protein C-terminal domain / DNA binding domain with preference for A/T rich regions / AT hook, DNA-binding motif / RuvB-like / RuvB-like, AAA-lid domain / RuvBL1/2, DNA/RNA binding domain / TIP49 P-loop domain / TIP49 AAA-lid domain / TIP49, P-loop domain / domain in helicases and associated with SANT domains / HSA domain / Helicase/SANT-associated domain / HSA domain profile. / : / SNF2-like, N-terminal domain superfamily / SNF2, N-terminal / SNF2-related domain / Actins signature 1. / Actin, conserved site / Actins signature 2. / Actin/actin-like conserved site / Actins and actin-related proteins signature. / Actin / Actin family / Actin / : / Histone H2A conserved site / Histone H2A signature. / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone 2A / Histone H2A / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Helicase conserved C-terminal domain / Histone H3 signature 1. / ATPase, nucleotide binding domain / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 domain / Histone-fold / helicase superfamily c-terminal domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ADENOSINE-5'-DIPHOSPHATE / PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / DNA / DNA (> 10) / DNA (> 100) / Zinc finger HIT domain-containing protein 1 / YEATS domain-containing protein 4 / Actin-like protein 6A / Histone H2B 1.1 / Histone H2A type 1 ...ADENOSINE-5'-DIPHOSPHATE / PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / DNA / DNA (> 10) / DNA (> 100) / Zinc finger HIT domain-containing protein 1 / YEATS domain-containing protein 4 / Actin-like protein 6A / Histone H2B 1.1 / Histone H2A type 1 / Actin, cytoplasmic 1 / Histone H4 / Histone H3.2 / Vacuolar protein sorting-associated protein 72 homolog / Chromatin remodeling protein SRCAP / Actin-related protein 6 / DNA methyltransferase 1-associated protein 1 / RuvB-like 2 / RuvB-like 1
Similarity search - Component
Biological speciesXenopus laevis (African clawed frog)
Homo sapiens (human)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 7.1 Å
AuthorsLouder, R.K. / Park, G.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) United States
CitationJournal: Sci Adv / Year: 2026
Title: Structural mechanism of histone H2A.Z exchange by human SRCAP-CFDP1 holoenzyme.
Authors: Giho Park / Carl Wu / Robert K Louder /
Abstract: The conserved yeast SWR1 and human SRCAP chromatin remodeling complexes catalyze exchange of nucleosomal histone H2A for H2A.Z, but the underlying mechanism has remained obscure. Here, we show that ...The conserved yeast SWR1 and human SRCAP chromatin remodeling complexes catalyze exchange of nucleosomal histone H2A for H2A.Z, but the underlying mechanism has remained obscure. Here, we show that histone exchange by SRCAP requires the transient activator CFDP1 and resolve nine cryo-electron microscopy structures of the SRCAP-CFDP1 holoenzyme that define the stepwise exchange mechanism. CFDP1 recognizes the conformation of the fully engaged SRCAP-nucleosome complex through interactions with multiple subunits-including direct contact with the ATPase domain-and induces conformational transitions that drive extensive DNA unwrapping, eviction of the H2A-H2B dimer, and insertion of the H2A.Z-H2B dimer, all without necessarily requiring hydrolysis of bound ATP. Collectively, these findings provide unprecedented insight into the mechanism of activator- and nucleotide-driven histone exchange from nucleosomal H2A to H2A.Z.
History
DepositionSep 2, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 12, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Helicase SRCAP
B: Vacuolar protein sorting-associated protein 72 homolog
C: Actin-related protein 6
D: Zinc finger HIT domain-containing protein 1
E: RuvB-like 1
F: RuvB-like 2
G: RuvB-like 1
H: RuvB-like 2
I: RuvB-like 1
J: RuvB-like 2
K: Actin-like protein 6A
L: Actin, cytoplasmic 1
M: Actin-like protein 6A
N: DNA methyltransferase 1-associated protein 1
O: YEATS domain-containing protein 4
Q: Histone H2A type 1
R: Histone H2B 1.1
S: Histone H2A type 1
T: Histone H2B 1.1
U: Histone H3.2
V: Histone H4
W: Histone H3.2
X: Histone H4
Y: DNA (285-MER)
Z: DNA (285-MER)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)1,258,08842
Polymers1,253,67925
Non-polymers4,41017
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 14 types, 23 molecules ABCDEGIFHJKMLNOQSRTUWVX

#1: Protein Helicase SRCAP / Domino homolog 2 / Snf2-related CBP activator


Mass: 343915.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW
References: UniProt: Q6ZRS2, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#2: Protein Vacuolar protein sorting-associated protein 72 homolog / Protein YL-1 / Transcription factor-like 1


Mass: 40658.363 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: Q15906
#3: Protein Actin-related protein 6 / hArp6 / hARPX


Mass: 45857.902 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: Q9GZN1
#4: Protein Zinc finger HIT domain-containing protein 1 / Cyclin-G1-binding protein 1 / Zinc finger protein subfamily 4A member 1 / p18 Hamlet


Mass: 17567.023 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: O43257
#5: Protein RuvB-like 1 / 49 kDa TATA box-binding protein-interacting protein / 49 kDa TBP-interacting protein / 54 kDa ...49 kDa TATA box-binding protein-interacting protein / 49 kDa TBP-interacting protein / 54 kDa erythrocyte cytosolic protein / ECP-54 / INO80 complex subunit H / Nuclear matrix protein 238 / NMP 238 / Pontin 52 / TIP49a / TIP60-associated protein 54-alpha / TAP54-alpha


Mass: 50296.914 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: Q9Y265, DNA helicase
#6: Protein RuvB-like 2 / 48 kDa TATA box-binding protein-interacting protein / 48 kDa TBP-interacting protein / 51 kDa ...48 kDa TATA box-binding protein-interacting protein / 48 kDa TBP-interacting protein / 51 kDa erythrocyte cytosolic protein / ECP-51 / INO80 complex subunit J / Repressing pontin 52 / Reptin 52 / TIP49b / TIP60-associated protein 54-beta / TAP54-beta


Mass: 51222.465 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: Q9Y230, DNA helicase
#7: Protein Actin-like protein 6A / 53 kDa BRG1-associated factor A / Actin-related protein Baf53a / ArpNbeta / BRG1-associated factor ...53 kDa BRG1-associated factor A / Actin-related protein Baf53a / ArpNbeta / BRG1-associated factor 53A / BAF53A / INO80 complex subunit K


Mass: 47509.812 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: O96019
#8: Protein Actin, cytoplasmic 1 / Beta-actin


Mass: 41782.660 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: P60709
#9: Protein DNA methyltransferase 1-associated protein 1 / DNMAP1 / DNMT1-associated protein 1


Mass: 53090.699 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: Q9NPF5
#10: Protein YEATS domain-containing protein 4 / Glioma-amplified sequence 41 / Gas41 / NuMA-binding protein 1 / NuBI-1 / NuBI1


Mass: 26541.537 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K-562 / Organ: BLOOD / Tissue: BONE MARROW / References: UniProt: O95619
#11: Protein Histone H2A type 1


Mass: 13907.163 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P06897
#12: Protein Histone H2B 1.1 / H2B1.1


Mass: 13848.097 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P02281
#13: Protein Histone H3.2 / Histone H3


Mass: 15303.930 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P84233
#14: Protein Histone H4


Mass: 11263.231 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P62799

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DNA chain , 2 types, 2 molecules YZ

#15: DNA chain DNA (285-MER)


Mass: 87851.664 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#16: DNA chain DNA (285-MER)


Mass: 88190.930 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

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Non-polymers , 4 types, 17 molecules

#17: Chemical ChemComp-AGS / PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-GAMMA-S / ADENOSINE 5'-(3-THIOTRIPHOSPHATE) / ADENOSINE 5'-(GAMMA-THIOTRIPHOSPHATE) / ADENOSINE-5'-DIPHOSPHATE MONOTHIOPHOSPHATE


Mass: 523.247 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C10H16N5O12P3S / Comment: ATP-gamma-S, energy-carrying molecule analogue*YM
#18: Chemical
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Mg
#19: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#20: Chemical
ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Comment: ADP, energy-carrying molecule*YM

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Details

Has ligand of interestN
Has protein modificationN

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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

Component
IDNameTypeEntity IDParent-IDSource
1SRCAP-nucleosome complexCOMPLEX#1-#160MULTIPLE SOURCES
2Endogenous human SRCAP complexCOMPLEX#1-#101NATURAL
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human) / Strain: K-562 / Cellular location: NUCLEOPLASM / Organ: BLOOD / Organelle: NUCLEUS / Tissue: BONE MARROW
Buffer solutionpH: 7.6
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: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1RELIONparticle selection
2PHENIX1.21_5207model refinement
13RELION3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 7.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 5605 / Symmetry type: POINT
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 467.72 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.002461321
ELECTRON MICROSCOPYf_angle_d0.535784296
ELECTRON MICROSCOPYf_chiral_restr0.04019493
ELECTRON MICROSCOPYf_plane_restr0.00679609
ELECTRON MICROSCOPYf_dihedral_angle_d20.439111039

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