ATP Synthase paper

Trey Dyer

FYS- Molecular Machines

Prof. Jed Macosko

2/12/07

The Body’s Rotary Based Generator- ATP Synthase

Mankind has been studying the human body since, well, the beginning of mankind. Over time, man has gradually come to grasp what makes our bodies move or our blood pump. In the last century or so, scientists have been making landmark discoveries such as cells and DNA. Theses discoveries have created sub-branches of biology including bionanotechnology. Bionanotechnology is the study of molecular machines inside the cell and how they work. Every cell in our body is made up of molecular machines. The potential of machines in bionanotechnology can shape and change our world. Eco-friendly machines such as the energy producing ATP synthase can - and hopefully - will be harnessed for the improvement of our environment. In order to fully harness machines such as ATP synthase humanity must first understand its structure and function. Understanding these concepts is crucial to the development of bionanotechnology.

In order to understand ATP synthase’s function and how to harness its power, we must first understand and grasp its structure. ATP synthase is found embedded in the membranes of micro-organisms such as bacteria, chloroplast (thylakoid membrane), and in the inner mitochondrial membrane of eukaryotic cells. It is a large “mushroom-shaped” enzyme. This portion of ATP synthase is water soluble. Its crystal structure has been deciphered where as the F₀ portion has not. It exists as a complex of at least 24 proteins, depending upon the organism.

ATP synthase is divided into two motor-like sections along an axel- the F₀ and F₁ motors. The F₁ motor is the part of the enzyme that is located on the outside of the membrane. It is sometimes called the “cap” of the mushroom shape. It is made up of 5 different types of subunits: 3a (alpha), 3b (beta), 1g (gamma), 1d (sigma), and 1e (epsilon). The three alpha and the three beta subunits form a ring of alternating subunits. This is what is known as the cap of the mushroom. This is the catalytic portion of ATP synthase. These six alternating subunits form a ring around the gamma subunit. The gamma subunit is the axel of the motor of ATP synthase extending down into the F₀ motor. The epsilon is connected to the gamma subunit towards the bottom of the axel where it disappears inside of the cell membrane. The sigma particle is connected to the top of the hexamer of alpha and beta particles. The sigma particle is connected to the stator which is used down in the F₀ portion of ATP synthase. The three beta subunits in the hexamer or “cap” of the mushroom of ATP are the binding sites where ATP is catalyzed. The F₁ motor is turned due in large part to the F₀ motor.

The F₀ motor is embedded in the membrane of the cell. It is made up of 3 subunits: a, b, and c. Six c subunits form yet another hexamer located in the cell membrane. This hexamer is formed around the very same gamma subunit or axel as the F₁ motor. These c subunits are strongly hydrophobic. The rotation of these six proteins rotates the gamma subunit, which in turn rotates the F₁ motor. Loosely connected on the outside of these three proteins is the a subunit. The translocation of protons takes places between the a subunit and the rotating c subunits. Connected to the a subunit is the b subunit. The b subunit is what’s known as the stator. It guides the protons in order for the electrochemical gradient to cause the F₀ motor to rotate or run. The b subunit connects to the sigma subunit of the F₁ motor which connects to the hexamer as well. The structure of ATP synthase is a complex structure of proteins essentially forming two motors connected through one axel. This structure enables ATP synthase to accomplish its true function- generating energy for the cell.

As stated earlier, ATP synthase is composed of two rotary type motors sharing the same axel. The question now is how do these two motors turn into one super-efficient generator. The first thing to understand with any motor is what its fuel is, what does it run on? The F₁ motor runs on ATP or the catalyzation of ATP. However, this motor is usually turned by the F₀ motor which causes the catalyzation of ATP. Producing ATP is this machine’s main purpose since ATP is the core source and form of energy used by nearly every organism in the body. The fuel for the F₀ motor is an electrochemical gradient created with the flow of protons across the cell membrane.

These motors are bidirectional. Cleavage of ATP can cause the F₁ motor to rotate and in turn creating an electrochemical gradient. Also, the movement of protons through the cell membrane can cause the F₀ motor to spin which in turn causes rotation in the F₁ motor and thus catalyzes the reaction that synthesizes ATP. It is essential to see how these two motors work together to make ATP synthase an effective generator.

The F₀ motor is the starting point of ATP synthesis. First the hexamer of c subunits must rotate to turn the gamma subunit, which turns the F₁ motor. The F₀ motor is driven by an electrochemical gradient of protons within the cell membrane. The stator of the F₀ motor, the b subunit, guides protons in the membrane in between the a and c subunits. This creates an electrochemical gradient, which in turn causes the hexamer of c subunits to rotate. This rotates the gamma subunit or axel, which in turn rotates the F₁ motor. The movement of protons across the membrane is due to a simple electrochemical gradient. The stator then guides some of these proton in between a and c, which leads to rotation.

The rotation of the F₀ motor also causes the rotation of the F₁ motor, which causes the catalyzation of ATP. When the gamma subunit is rotated, the active sites or beta subunits undergo a change in binding affinity for the reactants of the ATP catalyzation. These reactants are inorganic phosphate and ADP. The three sections of the hexamer (one alpha and one beta subunit) have different affinities to the nucleotides. One section, the loose section, binds the ADP and phosphate together. The second section, the tight section, then binds these reactants so tightly that ATP is formed. The third section, the open section, then releases the newly formed ATP. As the F₁ motor rotates, these sections of three change into these different affinity levels: loose changes to tight, tight to open, and open to loose again. ATP is then transported throughout the cell to where energy is needed. ATP synthase is now an effective generator that turns an electrochemical gradient into a viable source of energy in ATP. ATP works as an enzyme really. It catalyzes the following reaction: ATP^4- + H₂O <=> ADP^3- + P_i^2- + H⁺.

The central axel, the gamma subunit, of ATP Synthase rotates 50-100 times a second. Daily, the human body generates over 100 kg of ATP a day. The actual precise name for ATP synthase is ATP phosphohydrolase (H⁺-transporting). There are four main types of ATP synthase; all of which are very similar. A big difference, though, is the V-ATPase which can use Na⁺ or sodium to create its electrochemical gradient to run the F₀ motor. Overall, ATP synthase is an incredible machine with incredible powers.

ATP synthase is just one of many molecular machines that have the potential to change and shape the world. ATP synthase is a very complex and efficient motor and energy generator for the body. As technology advances and mankind continues to make breakthroughs in the field of bionanotechnology, ATP synthase will be an essential machine to harness because its endless possibilities. Mankind is in constant need of energy. Humanity continues to use up our resources and our environment in search of energy. If harnessed, a molecular machine such as ATP synthase could do wonders for mankind and the world around us.