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