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PMID:19748354

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Citation

Augustin, S, Gerdes, F, Lee, S, Tsai, FT, Langer, T and Tatsuta, T (2009) An intersubunit signaling network coordinates ATP hydrolysis by m-AAA proteases. Mol. Cell 35:574-85

Abstract

Ring-shaped AAA+ ATPases control a variety of cellular processes by substrate unfolding and remodeling of macromolecular structures. However, how ATP hydrolysis within AAA+ rings is regulated and coupled to mechanical work is poorly understood. Here we demonstrate coordinated ATP hydrolysis within m-AAA protease ring complexes, conserved AAA+ machines in the inner membrane of mitochondria. ATP binding to one AAA subunit inhibits ATP hydrolysis by the neighboring subunit, leading to coordinated rather than stochastic ATP hydrolysis within the AAA ring. Unbiased genetic screens define an intersubunit signaling pathway involving conserved AAA motifs and reveal an intimate coupling of ATPase activities to central AAA pore loops. Coordinated ATP hydrolysis between adjacent subunits is required for membrane dislocation of substrates, but not for substrate processing. These findings provide insight into how AAA+ proteins convert energy derived from ATP hydrolysis into mechanical work.

Links

PubMed PMC2744646 Online version:10.1016/j.molcel.2009.07.018

Keywords

ATP-Dependent Proteases; Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Adenosine Triphosphate/metabolism; Allosteric Regulation; Amino Acid Motifs; Amino Acid Sequence; Binding Sites; Catalytic Domain; Conserved Sequence; Energy Metabolism; Fungal Proteins/chemistry; Fungal Proteins/genetics; Fungal Proteins/metabolism; Humans; Hydrolysis; Kinetics; Metalloendopeptidases/chemistry; Metalloendopeptidases/genetics; Metalloendopeptidases/metabolism; Mitochondrial Membranes/enzymology; Models, Molecular; Molecular Sequence Data; Point Mutation; Protein Subunits; Signal Transduction; Structure-Activity Relationship; Substrate Specificity; Yeasts/enzymology; Yeasts/genetics; Yeasts/growth & development

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:AFG3

enables

GO:0016887: ATP hydrolysis activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:AFG3

enables

GO:0016887: ATP hydrolysis activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

  • has_input:(UniProtKB:P25348)|has_input:(UniProtKB:P00431)

Seeded From UniProt

complete

YEAST:YTA12

enables

GO:0005524: ATP binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:YTA12

enables

GO:0016887: ATP hydrolysis activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:YTA12

enables

GO:0016887: ATP hydrolysis activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

  • has_input:(UniProtKB:P25348)|has_input:(UniProtKB:P00431)

Seeded From UniProt

complete


See also

References

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