title: Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH.
abstract: FtsH, a member of the AAA family of proteins, is the only membrane ATP-dependent protease universally conserved in prokaryotes, and the only essential ATP-dependent protease in Escherichia coli. We investigated the mechanism of degradation by FtsH. Other well-studied ATP-dependent proteases use ATP to unfold their substrates. In contrast, both in vitro and in vivo studies indicate that degradation by FtsH occurs efficiently only when the substrate is a protein of low intrinsic thermodynamic stability. Because FtsH lacks robust unfoldase activity, it is able to use the protein folding state of substrates as a criterion for degradation. This feature may be key to its role in the cell and account for its ubiquitous distribution among prokaryotic organisms.
authors.affiliation: Department of Microbiology & Immunology, University of California, San Franscisco, San Franscisco, CA 94143, USA. lherman@itsa.ucsf.edu
authors.forename: Christophe
authors.initials: C
authors.lastname: Herman
authors.forename: Sumit
authors.initials: S
authors.lastname: Prakash
authors.forename: Chi Zen
authors.initials: CZ
authors.lastname: Lu
authors.forename: Andreas
authors.initials: A
authors.lastname: Matouschek
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gross
mesh_terms: D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D049452:Green Fluorescent Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012808:Sigma Factor; D013379:Substrate Specificity; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D012329:RNA, Bacterial; D011993:Recombinant Fusion Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C069774:heat-shock sigma factor 32; C096222:tmRNA; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli; D000251:Adenosine Triphosphatases