scholarly journals Analysis of Sequence Determinants of F1Fo-ATP Synthase in the N-terminal Region of α Subunit for Binding of δ Subunit

2004 ◽  
Vol 279 (24) ◽  
pp. 25673-25679 ◽  
Author(s):  
Joachim Weber ◽  
Alma Muharemagic ◽  
Susan Wilke-Mounts ◽  
Alan E. Senior
Keyword(s):  
Atp Synthase ◽  
Terminal Region ◽  
Α Subunit ◽  
F1fo Atp Synthase

scholarly journals Structure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis

2021 ◽  
Vol 118 (47) ◽  
pp. e2111899118
Author(s):  
Martin G. Montgomery ◽  
Jessica Petri ◽  
Tobias E. Spikes ◽  
John E. Walker
Keyword(s):  
Atp Synthase ◽  
Mycobacterium Smegmatis ◽  
Atp Hydrolysis ◽  
Terminal Region ◽  
Catalytic Cycle ◽  
Α Subunit ◽  
Antitubercular Drugs ◽  
Safe Mechanism ◽  
Fail Safe ◽  
Α Subunits

The structure has been determined by electron cryomicroscopy of the adenosine triphosphate (ATP) synthase from Mycobacterium smegmatis. This analysis confirms features in a prior description of the structure of the enzyme, but it also describes other highly significant attributes not recognized before that are crucial for understanding the mechanism and regulation of the mycobacterial enzyme. First, we resolved not only the three main states in the catalytic cycle described before but also eight substates that portray structural and mechanistic changes occurring during a 360° catalytic cycle. Second, a mechanism of auto-inhibition of ATP hydrolysis involves not only the engagement of the C-terminal region of an α-subunit in a loop in the γ-subunit, as proposed before, but also a “fail-safe” mechanism involving the b′-subunit in the peripheral stalk that enhances engagement. A third unreported characteristic is that the fused bδ-subunit contains a duplicated domain in its N-terminal region where the two copies of the domain participate in similar modes of attachment of the two of three N-terminal regions of the α-subunits. The auto-inhibitory plus the associated “fail-safe” mechanisms and the modes of attachment of the α-subunits provide targets for development of innovative antitubercular drugs. The structure also provides support for an observation made in the bovine ATP synthase that the transmembrane proton-motive force that provides the energy to drive the rotary mechanism is delivered directly and tangentially to the rotor via a Grotthuss water chain in a polar L-shaped tunnel.

How the N-terminal Domain of the OSCP Subunit of Bovine F1Fo-ATP Synthase Interacts with the N-terminal Region of an Alpha Subunit

2007 ◽  
Vol 368 (2) ◽  
pp. 310-318 ◽  
Author(s):  
Rodrigo J. Carbajo ◽  
Fiona A. Kellas ◽  
Ji-Chun Yang ◽  
Michael J. Runswick ◽  
Martin G. Montgomery ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Terminal Region ◽  
Alpha Subunit ◽  
F1fo Atp Synthase ◽  
Terminal Domain

Deletion of the natural inhibitory protein Inh1 in Ustilago maydis has no effect on the dimeric state of the F1FO-ATP synthase but increases the ATPase activity and reduces the stability

2021 ◽  
Vol 1862 (7) ◽  
pp. 148429
Author(s):  
Romero-Aguilar Lucero ◽  
Esparza-Perusquía Mercedes ◽  
Langner Thorsten ◽  
García-Cruz Giovanni ◽  
Feldbrügge Michael ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Atp Synthase ◽  
Ustilago Maydis ◽  
Inhibitory Protein ◽  
F1fo Atp Synthase ◽  
The Stability

scholarly journals Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 242
Author(s):  
Salvatore Nesci ◽  
Fabiana Trombetti ◽  
Alessandra Pagliarani ◽  
Vittoria Ventrella ◽  
Cristina Algieri ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Ros Generation ◽  
Protonmotive Force ◽  
Mitochondrial Oxidative Phosphorylation ◽  
F1fo Atp Synthase ◽  
Functional Changes ◽  
Age Related ◽  
Mitochondrial Functions

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

scholarly journals The spatio-temporal organization of mitochondrial F1FO ATP synthase in cristae depends on its activity mode

2020 ◽  
Vol 1861 (1) ◽  
pp. 148091 ◽  
Author(s):  
Kirill Salewskij ◽  
Bettina Rieger ◽  
Frances Hager ◽  
Tasnim Arroum ◽  
Patrick Duwe ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Temporal Organization ◽  
F1fo Atp Synthase ◽  
Activity Mode ◽  
Spatio Temporal

scholarly journals Targeting Mycobacterial F-ATP Synthase C-Terminal α Subunit Interaction Motif on Rotary Subunit γ

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1456
Author(s):  
Amaravadhi Harikishore ◽  
Chui-Fann Wong ◽  
Priya Ragunathan ◽  
Dennis Litty ◽  
Volker Müller ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Atp Hydrolysis ◽  
Atp Synthesis ◽  
Membrane Vesicles ◽  
Α Subunit ◽  
Rotational States ◽  
C Terminus ◽  
Inverted Membrane Vesicles ◽  
Hydrolysis Of ◽  
Micromolar Range

Mycobacteria regulate their energy (ATP) levels to sustain their survival even in stringent living conditions. Recent studies have shown that mycobacteria not only slow down their respiratory rate but also block ATP hydrolysis of the F-ATP synthase (α3:β3:γ:δ:ε:a:b:b’:c9) to maintain ATP homeostasis in situations not amenable for growth. The mycobacteria-specific α C-terminus (α533-545) has unraveled to be the major regulative of latent ATP hydrolysis. Its deletion stimulates ATPase activity while reducing ATP synthesis. In one of the six rotational states of F-ATP synthase, α533-545 has been visualized to dock deep into subunit γ, thereby blocking rotation of γ within the engine. The functional role(s) of this C-terminus in the other rotational states are not clarified yet and are being still pursued in structural studies. Based on the interaction pattern of the docked α533-545 region with subunit γ, we attempted to study the druggability of the α533-545 motif. In this direction, our computational work has led to the development of an eight-featured α533-545 peptide pharmacophore, followed by database screening, molecular docking, and pose selection, resulting in eleven hit molecules. ATP synthesis inhibition assays using recombinant ATP synthase as well as mycobacterial inverted membrane vesicles show that one of the hits, AlMF1, inhibited the mycobacterial F-ATP synthase in a micromolar range. The successful targeting of the α533-545-γ interaction motif demonstrates the potential to develop inhibitors targeting the α site to interrupt rotary coupling with ATP synthesis.

scholarly journals Impact of F1Fo-ATP-synthase dimer assembly factors on mitochondrial function and organismic aging

2018 ◽  
Vol 5 (4) ◽  
pp. 198-207 ◽  
Author(s):  
Nadia G Rampello ◽  
Maria Stenger ◽  
Benedikt Westermann ◽  
Heinz D Osiewacz
Keyword(s):  
Atp Synthase ◽  
Mitochondrial Function ◽  
F1fo Atp Synthase ◽  
Assembly Factors
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