PMID:11251810
| Citation |
Karata, K, Verma, CS, Wilkinson, AJ and Ogura, T (2001) Probing the mechanism of ATP hydrolysis and substrate translocation in the AAA protease FtsH by modelling and mutagenesis. Mol. Microbiol. 39:890-903 |
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| Abstract |
We have built a homology model of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli based on the crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein. The resulting model of the hexameric ring of the ATP-bound form of the AAA ATPase suggests a plausible mechanism of ATP binding and hydrolysis, in which invariant residues of Walker motifs A and B and the second region of homology, characteristic of the AAA ATPases, play key roles. The importance of these invariant residues was confirmed by site-directed mutagenesis. Further modelling suggested a mechanism by which ATP hydrolysis alters the conformation of the loop forming the central hole of the hexameric ring. It is proposed that unfolded polypeptides are translocated through the central hole into the protease chamber upon cycles of ATP hydrolysis. Degradation of polypeptides by FtsH is tightly coupled to ATP hydrolysis, whereas ATP binding alone is sufficient to support the degradation of short peptides. Furthermore, comparative structural analysis of FtsH and a related ATPase, HslU, reveals interesting similarities and differences in mechanism. |
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| Keywords |
ATP-Dependent Proteases; Adenosine Diphosphate/metabolism; Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/metabolism; Adenosine Triphosphate/metabolism; Amino Acid Sequence; Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Caseins/metabolism; Computer Simulation; Escherichia coli Proteins; Humans; Hydrolysis; Membrane Proteins/chemistry; Membrane Proteins/metabolism; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Peptides/metabolism; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Substrate Specificity |
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