ATP-dependent proteases differ substantially in their ability to unfold globular proteins.
ATP-dependent proteases control the concentrations of hundreds of regulatory proteins and remove damaged or misfolded proteins from cells. They select their substrates primarily by recognizing sequence motifs or covalent modifications. Once a substrate is bound to the protease, it has to be unfolded and translocated into the proteolytic chamber to be degraded. Some proteases appear to be promiscuous, degrading substrates with poorly defined targeting signals, which suggests that selectivity may be controlled at additional levels. Here we compare the abilities of representatives from all classes of ATP-dependent proteases to unfold a model substrate protein and find that the unfolding abilities range over more than 2 orders of magnitude. We propose that these differences in unfolding abilities contribute to the fates of substrate proteins and may act as a further layer of selectivity during protein destruction.
Koodathingal
Prakash
P
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Jaffe
Neil E
NE
Kraut
Daniel A
DA
Prakash
Sumit
S
Fishbain
Susan
S
Herman
Christophe
C
Matouschek
Andreas
A
D049069:ATP-Dependent Proteases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry*; D001407:Bacillus / Q000201:enzymology*; D001426:Bacterial Proteins; D001671:Biochemistry / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry; D007700:Kinetics; D049070:Protease La / Q000737:chemistry; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012260:Ribonucleases / Q000737:chemistry; D013816:Thermodynamics
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D000255:Adenosine Triphosphate; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli; C483567:Lon protein, E coli; D049070:Protease La