F-ATPase · Towards a Complete Quantitative Model of the FOF1 ATP Synthase
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-03-01 → 2018-02-28
- EU contribution
- €171,461
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Towards a Complete Quantitative Model of the FOF1 ATP Synthase
Adenosine triphosphate (ATP) is the energy-currency of cells. This small molecule “stores” energy in a form that is readily consumable by the majority of biomolecular machines. It is synthesized primarily by the mitochondrial F-ATPase, a protein complex. We sought to understand the kinetics and thermodynamics by which this machine operates by building a numerical model to explain the function of this biomotor. This knowledge is crucial to understanding cellular energy production. We also studied an ATP-driven molecule that harnesses this energy to perform a task crucial to cell vitality. This protein (ABCE1, the sole member of the ATP Binding Cassette family E) utilizes energy from the hydrolysis of ATP and the release of its constituent parts. ABCE1 is responsible for turnover of the ribosomal machinery (which itself is the machinery that makes protein biomolecules). Studying these molecules is crucial to understanding how energy is stored and used by cells, including in the human mitochondria. This also includes understanding the differences between human and bacterial forms of these cellular components—which may facilitate our ability to exploit these differences. Additionally, our study will help us better understand how biomolecular systems produce asymmetric responses from highly symmetric systems, which is vital to developing and designing future nano-systems that can use rotary motors or be fueled by ATP.
Data: CORDIS, © European Union
Project objective
The FOF1-ATPase is a complex nanomotor that synthesizes nearly 90% of the ATP made during cellular respiration. It consists of two coupled rotary motors: an integral membrane complex driven by proton flow across lipid bilayers (FO) and an enzymatic complex that converts ADP and inorganic phosphate to ATP (F1). The rotational portion of these motors acts as a camshaft, inducing conformational changes that lead to ATP synthesis in the F1 motor’s three functional catalytic sites. The F1 motor can perform ATP synthesis in the absence of FO, and it can also work in reverse, hydrolyzing ATP to pump protons against an established gradient. Over the last 30 years many important aspects of this motor’s function have been elucidated by careful biochemical work and further understood by clever biophysical experiments. However, there is still not a complete, quantitative description of the whole thermodynamic cycle—one that fully describes the interactions between all three separate catalytic sites and accounts for the need to exchange ATP (found abundantly) for the relatively sparse ADP.
Original text from CORDIS.
Participants
- MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENCoordinatorGermany
Links
Data: CORDIS, © European Union