An intramolecular route for coupling ATPase activity in AAA+ proteins for transcription activation.
AAA+ proteins (ATPases associated with various cellular activities) contribute to many cellular processes and typically function as higher order oligomers permitting the coordination of nucleotide hydrolysis for functional output, which leads to substrate remodeling. The precise mechanisms that enable the relay of nucleotide hydrolysis to their specific functional outputs are largely unknown. Here we use PspF, a specialized AAA+ protein required for enhancer-dependent transcription activation in Escherichia coli, as a model system to address this question. We demonstrate that a conserved asparagine is involved in internal organization of the oligomeric ring, regulation of ATPase activity by "trans" factors, and optimizing substrate remodeling. We provide evidence that the spatial relationship between the asparagine residue and the Walker B motif is one key element in the conformational signaling pathway that leads to substrate remodeling. Such functional organization most likely applies to other AAA+ proteins, including Ltag (simian virus 40), Rep40 (Adeno-associated virus-2), and p97 (Mus musculus) in which the asparagine to Walker B motif relationship is conserved.
Joly
Nicolas
N
Division of Biology, Sir Alexander Fleming Building, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
Burrows
Patricia C
PC
Buck
Martin
M
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D015533:Transcriptional Activation; D001616:beta-Galactosidase / Q000378:metabolism
D029968:Escherichia coli Proteins; C098954:PspF protein, E coli; D015534:Trans-Activators; D001616:beta-Galactosidase; D000251:Adenosine Triphosphatases