title: FtsH cleavage of non-native conformations of proteins.
abstract: FtsH is a peculiar prokaryotic protease with low unfoldase activity. Different reports have proposed that FtsH substrates could be either tagged proteins or proteins of low stability. We show here that FtsH degradation of 31 point mutants of Anabaena apoflavodoxin is inversely proportional to their conformational stabilities, and that the same applies to other substrate proteins. In contrast, highly stable proteins such as GST and holoflavodoxin are not degraded at all. Attempts to identify sequence tags signaling for degradation in apoflavodoxin fragments have been unsuccessful. Apoflavodoxin adopts three conformations: native, partly unfolded and fully unfolded. It is revealing that degradation of the 31 variants is proportional to the molar fraction of fully unfolded molecules and inversely proportional to the fraction of stable apoflavodoxin molecules. This indicates that FtsH, rather than unfolding the protein, acts on the fraction that is already unfolded.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza 50009, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ayuso-Tejedor
authors.forename: Shingo
authors.initials: S
authors.lastname: Nishikori
authors.forename: Takashi
authors.initials: T
authors.lastname: Okuno
authors.forename: Teru
authors.initials: T
authors.lastname: Ogura
authors.forename: Javier
authors.initials: J
authors.lastname: Sancho
mesh_terms: D049069:ATP-Dependent Proteases / Q000378:metabolism*; D000595:Amino Acid Sequence; D017033:Anabaena / Q000201:enzymology; D001059:Apoproteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D005418:Flavodoxin / Q000378:metabolism*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D001059:Apoproteins; D001426:Bacterial Proteins; D005418:Flavodoxin; C026932:apoflavodoxin; D049069:ATP-Dependent Proteases