8H3H
Human ATAD2 Walker B mutant, ATP state
Summary for 8H3H
| Entry DOI | 10.2210/pdb8h3h/pdb |
| EMDB information | 34468 |
| Descriptor | ATPase family AAA domain-containing protein 2, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total) |
| Functional Keywords | histone chaperone, aaa+ atpase, gene regulation |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 565105.54 |
| Authors | |
| Primary citation | Cho, C.,Ganser, C.,Uchihashi, T.,Kato, K.,Song, J.J. Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication. Commun Biol, 6:993-993, 2023 Cited by PubMed 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 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. PubMed: 37770645DOI: 10.1038/s42003-023-05373-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.15 Å) |
Structure validation
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