The Saccharomyces cerevisiae Yta7 ATPase hexamer contains a unique bromodomain tier that functions in nucleosome disassembly

Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication

“…Two major structural differences between human ATAD2 and its yeast homologs 19 , 37 emerge from this study, which suggests differences in their respective roles and mechanisms. Firstly, the absence of interlocking knob-hole interactions in ATAD2, when compared to Abo1 and Yta7 indicates that the hexamer formed by human ATAD2 is more dynamic and labile and can more readily disassemble into monomers.…”

“…Bromodomains, linker arms, and C-terminal linker domains were not identified in our maps, likely due to the high disorder and/or flexibility of these domains relative to the AAA+ domains. However, based on similarities with Abo1 19 and Yta7 37 and the presence of additional density near the top surface of the AAA+ ring in 2D class averages, we propose a schematic of ATAD2 domain organization where the bromodomains and C-terminal linker domains are positioned near the top surface of the AAA+ ring (Fig. 1f ).…”

“…Together, these lines of evidence imply that the N-terminal LD acts as a brake that maintains ATAD2 in an autoinhibited state thus preventing premature ATPase activation. Interestingly, the N-terminal LD was also proposed as a gate loop in recent structures of the ATAD2 yeast homolog, Yta7, based on its nucleotide-dependent conformational change near the nucleotide entry pocket 37 . Although the gate loop in Yta7 is not docked to seam subunits as in ATAD2 (discussed in more detail below), the idea of the N-terminal LD as a gating element that regulates nucleotide hydrolysis and exchange might be conserved among species.…”

“…This is supported by our biochemical findings which show that wild type ATAD2 assumes a wide range of oligomeric forms, in contrast to Abo1 which remains a stable hexamer regardless of nucleotide condition. Secondly, the N-terminal LD is observed to wedge between subunits in the ATAD2 structure but is unobserved in the Abo1 or Yta7 structures 19 , 37 . Although the LD may play a nucleotide gating role in all homologs, divergences in the N-terminal LD and the interacting bromo- and CTL domains, as well as differences in hexameric organization could explain why the LD acts as a brake only in ATAD2.…”