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The AAA+ superfamily of functionally diverse proteins.

Snider J, Thibault G, Houry WA - Genome Biol. (2008)

Bottom Line: The AAA+ superfamily is a large and functionally diverse superfamily of NTPases that are characterized by a conserved nucleotide-binding and catalytic module, the AAA+ module.Members are involved in an astonishing range of different cellular processes, attaining this functional diversity through additions of structural motifs and modifications to the core AAA+ module.

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Affiliation: Department of Biochemistry, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.

ABSTRACT

Summary: The AAA+ superfamily is a large and functionally diverse superfamily of NTPases that are characterized by a conserved nucleotide-binding and catalytic module, the AAA+ module. Members are involved in an astonishing range of different cellular processes, attaining this functional diversity through additions of structural motifs and modifications to the core AAA+ module.

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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].
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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].

Mentions: Different clades and families within the AAA+ superfamily also display unique structural modifications to the core AAA+ module, many of which possibly play a role in directing these families towards specific functions. Members of the clamp loader clade of the HEC group (see Table 1) best represent the 'basic' or 'core' AAA+ module, generally containing little to no modification [1]. The clamp loaders serve as mobile structures to which DNA polymerase core enzyme can be mounted during the process of DNA replication. The RFC1 protein of Saccharomyces cerevisiae shown in Figure 2 exemplifies this clade. Figure 2 also shows the AAA+ module structures of selected members of different clades/families, highlighting distinct structural modifications.


The AAA+ superfamily of functionally diverse proteins.

Snider J, Thibault G, Houry WA - Genome Biol. (2008)

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].
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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].
Mentions: Different clades and families within the AAA+ superfamily also display unique structural modifications to the core AAA+ module, many of which possibly play a role in directing these families towards specific functions. Members of the clamp loader clade of the HEC group (see Table 1) best represent the 'basic' or 'core' AAA+ module, generally containing little to no modification [1]. The clamp loaders serve as mobile structures to which DNA polymerase core enzyme can be mounted during the process of DNA replication. The RFC1 protein of Saccharomyces cerevisiae shown in Figure 2 exemplifies this clade. Figure 2 also shows the AAA+ module structures of selected members of different clades/families, highlighting distinct structural modifications.

Bottom Line: The AAA+ superfamily is a large and functionally diverse superfamily of NTPases that are characterized by a conserved nucleotide-binding and catalytic module, the AAA+ module.Members are involved in an astonishing range of different cellular processes, attaining this functional diversity through additions of structural motifs and modifications to the core AAA+ module.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.

ABSTRACT

Summary: The AAA+ superfamily is a large and functionally diverse superfamily of NTPases that are characterized by a conserved nucleotide-binding and catalytic module, the AAA+ module. Members are involved in an astonishing range of different cellular processes, attaining this functional diversity through additions of structural motifs and modifications to the core AAA+ module.

Show MeSH
Related in: MedlinePlus