Cell complexity: ATPase multiple functions (Introduction)

by David Turell , Thursday, August 22, 2019, 06:13 (1922 days ago) @ David Turell

Energy machines in cells, driving flagella, etc.:

https://evolutionnews.org/2019/08/design-for-atp-extends-beyond-the-rotary-engine/

"A paper in PNAS by Kwangho Nam and Martin Karplus explores “Insights into the origin of the high energy-conversion efficiency of F1-ATPase.” And do they mean efficiency!

"F1-ATPase is a small motor protein, composed of 3 α- and 3 β-subunits that surround a central γ-subunit. The β-subunits alternate cyclically between 2 major conformational states to produce the rotation of the γ-subunit. Although the rotation on the microsecond timescale is powered by the differential binding of ATP and its hydrolysis products ADP and HPO42−, there is near-100% conversion efficiency of the free energy of ATP hydrolysis, which occurs on the picosecond timescale. The free-energy profile constructed for the 360° rotation cycle shows that F1-ATPase achieves its high energy-conversion efficiency by elegantly separating fast catalytic events, which involve small local conformational changes, from the slow binding/release of ligands involved in the large conformational change.

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"How can ATP synthase achieve near-100% efficiency, such that the energy from one process is completely converted to another, with almost zero loss? Thermal escape is too rapid to overcome, even at this scale.

"The authors found an “elegant separation” between two catalytic events that operate at timescales differing by six orders of magnitude. This apparently gives the motor time for conformational changes in the protein parts and release of products that drive rotation of the rotor. The elasticity or “stiffness” in the rotor also contributes to efficient energy conversion. So finely tuned is each part of the engine to the others, the free energy “changes linearly along the rotation coordinate.” This means that the motor “functions near the maximum possible efficiency.”

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"A description in BioArchitecture states, “Bacterial enzymes have been clocked to run at up to 42,000 rpm under low load, though for intact enzymes under physiological conditions the number is closer to 6000 rpm.” A typical car starts redlining at that value. High-performance racing cars peak a little above 10,000 rpm. Isn’t it amazing what chance can do?

"Molecular machines, like the rotary ATPases described here, seem to have much in common with man-made machines. However, the analogies hold only to a certain point and are in large parts not fully understood. What is evident is that several billion years of evolution have resulted in biological motors that are unsurpassed in efficiency, fine-tuning to their environment and sustainability.

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"The first paper was concerned primarily with the F1 part of ATP synthase, where ATP synthesis or hydrolysis occurs. The F0 part, where protons drive rotation of a carousel-like wheel, also contributes to the efficiency. It drives the γ-subunit that acts like a camshaft. The camshaft extends into the F1 part, in effect “snapping” ADP and phosphate together to form ATP in three stages per revolution: synthesis, ejection, and loading.

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"They solved high-resolution cryo–electron microscopy structures of the ATP synthase complex, extracting 13 rotational substates. This collection of structures revealed that the rotation of the Fo ring and central stalk is coupled with partial rotations of the F1 head. This flexibility may enable the head to better couple continuous rotation with discrete ATP synthesis events.

"An animation in the paper shows the F1 domain undergoing a rocking motion back and forth as the F0 domain rotates around continuously. The rocking motion is achieved by means of another finely tuned protein called OSCP. The beauty of this solution allows for F1 heads to accommodate differing sizes of F0 rotors through a universal joint.

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" Some animations of ATP synthesis show the products ejecting from the machine, as if they just fly off into the air. Actually, transport of ADP into and ATP out of the motor are also tightly regulated. The “mitochondrial ADP/ATP carrier” (AAC) is right there, like a UPS truck, to get the products where they are needed.

Inside the mitochondrion, as reported here before, there are inner and outer membranes, with TIM and TOM transporters that control what enters and exits.

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"Translating this into a more everyday analogy, the AAC truck driver keeps an eye on how many protons are leaking out into the cytoplasm, and calls back to the engine house to have them slow down production. When the truck driver can keep up with production, proton leakage is small (negative regulation). But when more protons leak out, the driver warns that ATP synthase is outpacing demand.

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"As more details of ATP synthase come to light, more and more fine-tuning appears. The synthesis of ATP, necessary from the very start of metabolic life, is now seen to be phenomenally efficient and masterfully regulated by multiple parts working together. Just give chance billions of years, and miracles like this can happen. Not."

Comment: Better machines than humans can create.