Figure 2.

Structures of the AAA+ modules of selected superfamilymembers (see Table 1). The core αβα nucleotide-binding domains are shown in green (α-helices and random coil) and blue (β-strands). The small, α-helical domain of each AAA+ module is shown in purple. The canonical AAA+ module structure is exemplified by that of RFC1, which is shown in the center. (a) Representative members of the extended AAA group [6]. The FtsH AAA+ module from Thermus thermophilus (left, PDB 2DHR) contains an additional small helix (pink) downstream of the second β-strand, which is characteristic of the classical AAA clade [1,15]. The function of FtsH is discussed in the text. The Rvb AAA+ module, represented by human Rvb1 (center, PDB 2C90), contains a β-sheet-rich insert (pink) upstream of the Walker B motif and an additional small helix (yellow) downstream of the second β-strand of the core domain [1]. The β-sheet-rich insert is proposed to play a role in sequence-independent DNA and RNA binding [66]. The amino-terminal (D1) AAA+ modules of ClpB-type proteins are represented by a structure from T. thermophilus (right, PDB 1QVR). These proteins contain a long, leucine-rich coiled-coil propeller domain (pink) inserted into the small α-helical domain [67]. This propeller domain is proposed to play a role in interdomain communication and protein disaggregation, possibly acting as a molecular crowbar [67]. (b) Representative members of the HEC group [6]. The RFC1 AAA+ module from S. cerevisiae (center, PDB 1SXJ) represents a 'classical' AAA+ module containing no structural modifications and typifies the clamp loader clade to which it belongs [1,68]. The DnaA AAA+ module from Aquifex aeolicus (left, PDB 2HCB2HCB) contains an insert of two equal-sized helices (pink) after the second β-strand and is representative of the initiation clade [9]. The RuvB AAA+ module from T. thermophilus (right, PDB 1HQC) contains a β-hairpin insert (pink) between sensor 1 and its preceding helix [35]. This insert is characteristic of the RuvB family and is known to be important for the interaction of RuvB with RuvA in the resolution of Holliday junctions in DNA recombination [69,70]. The function of RuvB is discussed in the text. (c) Representatives of the PACTT group. Members of this group all contain a β-hairpin insert (cyan, shown in all three structures) between the sensor 1 strand and the preceding helix [1]. The BchI AAA+ module from Rhodobacter capsulatus Mg2+ chelatase (left, PDB 1G8P) belongs to the helix-2 insert clade. Members of this clade contain a small insert of two β-strands flanking a small α-helix (pink) in helix 2 of the αβα core domain and a long helical insert (yellow) between the fifth β-strand of the core domain and the small α-helical domain [1,24]. BchI proteins also contain a long, highly conserved β-hairpin insert (orange) upstream of the second β-strand of the core domain [24]. The function of BchI is discussed in the text. The carboxy-terminal ClpA AAA+ module (D2) from Escherichia coli (center, PDB 1KSF) [71] and the HslU AAA+ module from E. coli (right, PDB 1G4A) [72] are both representative members of the HCL clade, whose members are involved in protein unfolding and degradation. These structures contain an extended loop (pink) between the second core β-strand and the following helix [1] and a two or three stranded β-sheet insert (yellow) in the small α-helical domain of the AAA+ module, both characteristic of this clade. In addition, HslU family members contain an additional 130 amino acid I domain (orange, only part of the domain is resolved in the crystal structure) inserted into the core αβα domain of the AAA+ module, which is proposed to play a role in substrate recognition and unfolding [73].

Snider et al. Genome Biology 2008 9:216   doi:10.1186/gb-2008-9-4-216
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