Proteolysis mediated by the membrane-integrated ATP-dependent protease FtsH has a unique nonlinear dependence on ATP hydrolysis rates.
AAA+ protease
ATP hydrolysis rate
FtsH
cooperativity
membrane protein degradation
membrane protein folding
membrane protein quality control
steric trapping
Journal
Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
27
02
2019
accepted:
17
04
2019
pubmed:
23
4
2019
medline:
14
4
2020
entrez:
23
4
2019
Statut:
ppublish
Résumé
ATPases associated with diverse cellular activities (AAA+) proteases utilize ATP hydrolysis to actively unfold native or misfolded proteins and translocate them into a protease chamber for degradation. This basic mechanism yields diverse cellular consequences, including the removal of misfolded proteins, control of regulatory circuits, and remodeling of protein conformation. Among various bacterial AAA+ proteases, FtsH is only membrane-integrated and plays a key role in membrane protein quality control. Previously, we have shown that FtsH has substantial unfoldase activity for degrading membrane proteins overcoming a dual energetic burden of substrate unfolding and membrane dislocation. Here, we asked how efficiently FtsH utilizes ATP hydrolysis to degrade membrane proteins. To answer this question, we measured degradation rates of the model membrane substrate GlpG at various ATP hydrolysis rates in the lipid bilayers. We find that the dependence of degradation rates on ATP hydrolysis rates is highly nonlinear: (i) FtsH cannot degrade GlpG until it reaches a threshold ATP hydrolysis rate; (ii) after exceeding the threshold, the degradation rates steeply increase and saturate at the ATP hydrolysis rates far below the maxima. During the steep increase, FtsH efficiently utilizes ATP hydrolysis for degradation, consuming only 40-60% of the total ATP cost measured at the maximal ATP hydrolysis rates. This behavior does not fundamentally change against water-soluble substrates as well as upon addition of the macromolecular crowding agent Ficoll 70. The Hill analysis shows that the nonlinearity stems from coupling of three to five ATP hydrolysis events to degradation, which represents unique cooperativity compared to other AAA+ proteases including ClpXP, HslUV, Lon, and proteasomes.
Identifiants
pubmed: 31008538
doi: 10.1002/pro.3629
pmc: PMC6567685
doi:
Substances chimiques
Escherichia coli Proteins
0
Adenosine Triphosphate
8L70Q75FXE
ATP-Dependent Proteases
EC 3.4.21.-
FtsH protein, E coli
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1262-1275Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM118685
Pays : United States
Organisme : NIH HHS
ID : R01GM118685
Pays : United States
Informations de copyright
© 2019 The Protein Society.
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