[English] 日本語
![](img/lk-miru.gif)
- EMDB-36666: Human ATAD2 Walker B mutant-H3/H4K5Q complex, ATP state (Class II) -
+
Open data
-
Basic information
Entry | ![]() | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Human ATAD2 Walker B mutant-H3/H4K5Q complex, ATP state (Class II) | ||||||||||||||||||
![]() | |||||||||||||||||||
![]() |
| ||||||||||||||||||
![]() | Histone chaperone / AAA+ ATPase / GENE REGULATION | ||||||||||||||||||
Function / homology | ![]() nucleosome disassembly / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transcription initiation-coupled chromatin remodeling / nucleosome assembly / histone binding / chromatin binding / positive regulation of DNA-templated transcription / ATP hydrolysis activity / extracellular exosome ...nucleosome disassembly / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transcription initiation-coupled chromatin remodeling / nucleosome assembly / histone binding / chromatin binding / positive regulation of DNA-templated transcription / ATP hydrolysis activity / extracellular exosome / nucleoplasm / ATP binding / nucleus Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.34 Å | ||||||||||||||||||
![]() | Cho C / Song J | ||||||||||||||||||
Funding support | ![]()
| ||||||||||||||||||
![]() | ![]() Title: Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication. Authors: Carol Cho / Christian Ganser / Takayuki Uchihashi / Koichi Kato / Ji-Joon Song / ![]() ![]() Abstract: ATAD2 is a non-canonical ATP-dependent histone chaperone and a major cancer target. Despite widespread efforts to design drugs targeting the ATAD2 bromodomain, little is known about the overall ...ATAD2 is a non-canonical ATP-dependent histone chaperone and a major cancer target. Despite widespread efforts to design drugs targeting the ATAD2 bromodomain, little is known about the overall structural organization and regulation of ATAD2. Here, we present the 3.1 Å cryo-EM structure of human ATAD2 in the ATP state, showing a shallow hexameric spiral that binds a peptide substrate at the central pore. The spiral conformation is locked by an N-terminal linker domain (LD) that wedges between the seam subunits, thus limiting ATP-dependent symmetry breaking of the AAA+ ring. In contrast, structures of the ATAD2-histone H3/H4 complex show the LD undocked from the seam, suggesting that H3/H4 binding unlocks the AAA+ spiral by allosterically releasing the LD. These findings, together with the discovery of an inter-subunit signaling mechanism, reveal a unique regulatory mechanism for ATAD2 and lay the foundation for developing new ATAD2 inhibitors. | ||||||||||||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 7.9 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 15.6 KB 15.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 5.7 KB | Display | ![]() |
Images | ![]() | 25 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Others | ![]() ![]() | 80.7 MB 80.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8juyMC ![]() 8h3hC ![]() 8juwC ![]() 8juzC C: citing same article ( M: atomic model generated by this map |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #1
File | emd_36666_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_36666_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : ATAD2
Entire | Name: ATAD2 |
---|---|
Components |
|
-Supramolecule #1: ATAD2
Supramolecule | Name: ATAD2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: ATPase family AAA domain-containing protein 2
Macromolecule | Name: ATPase family AAA domain-containing protein 2 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO EC number: Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 93.690406 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DRMKIGASLA DVDPMQLDSS VRFDSVGGLS NHIAALKEMV VFPLLYPEVF EKFKIQPPRG CLFYGPPGTG KTLVARALAN ECSQGDKRV AFFMRKGADC LSKWVGESER QLRLLFDQAY QMRPSIIFFD QIDGLAPVRS SRQDQIHSSI VSTLLALMDG L DSRGEIVV ...String: DRMKIGASLA DVDPMQLDSS VRFDSVGGLS NHIAALKEMV VFPLLYPEVF EKFKIQPPRG CLFYGPPGTG KTLVARALAN ECSQGDKRV AFFMRKGADC LSKWVGESER QLRLLFDQAY QMRPSIIFFD QIDGLAPVRS SRQDQIHSSI VSTLLALMDG L DSRGEIVV IGATNRLDSI DPALRRPGRF DREFLFSLPD KEARKEILKI HTRDWNPKPL DTFLEELAEN CVGYCGADIK SI CAEAALC ALRRRYPQIY TTSEKLQLDL SSINISAKDF EVAMQKMIPA SQRAVTSPGQ ALSTVVKPLL QNTVDKILEA LQR VFPHAE FRTNKTLDSD ISCPLLESDL AYSDDDVPSV YENGLSQKSS HKAKDNFNFL HLNRNACYQP MSFRPRILIV GEPG FGQGS HLAPAVIHAL EKFTVYTLDI PVLFGVSTTS PEETCAQVIR EAKRTAPSIV YVPHIHVWWE IVGPTLKATF TTLLQ NIPS FAPVLLLATS DKPHSALPEE VQELFIRDYG EIFNVQLPDK EERTKFFEDL ILKQAAKPPI SKKKAVLQAL EVLPVA PPP EPRSLTAEEV KRLEEQEEYA PSYYHVMPKQ NSTLVGDKRS DPEQNEKLKT PSTPVACSTP AQLKRKIRKK SNWYLGT IK KRRKISQAKD DSQNAIDHKI ESDTEETQDT SVDHNETGNT GESSVEENEK QQNASESKLE LRNNSNTCNI ENELEDSR K TTACTELRDK IACNGDASSS QIIHISDENE GKEMCVLRMT QPTPSLVVDH ERLKNLLKTV VKKSQNYNIF QLENLYAVI SQCIYRHRKD HDKTSLIQKM EQEVENFSCS R UniProtKB: ATPase family AAA domain-containing protein 2, ATPase family AAA domain-containing protein 2, ATPase family AAA domain-containing protein 2 |
-Macromolecule #2: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 1 / Formula: ADP |
---|---|
Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ![]() ChemComp-ADP: |
-Macromolecule #3: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 5 / Formula: ATP |
---|---|
Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |