Intro to ATP Synthase and Modeling



The Process:

ATP Synthase is the process within the mitochondria of a cell by which a rotary engine uses the potential difference across the bilipid layer to power a chemical transformation of ADP into ATP. Wow, that's a mouthful, isn't it? The process, though as complicated as it sounds, can be simplified into a few steps and two pieces. Mitochondria, the powerhouses of cells, exist in a fluid within the human body. They have a wall (a "bilipid layer") which bounds them on all sides. Because of a difference in sodium and potassium ion concentrations a potential can be created. The potential can even be altered to a desired value by changing the ion concentrations. This process is one which uses that difference in potential to the cells' advantage.
ADP Picture

The positive ions try to move to a lower potential, and the negative ions try to move to a higher one, thus creating a force which is used to spin the rotor. As shown in one of the movies below, as the rotor spins the bottom section opens and closes special sections which do the actual work. When they open they take in ADP (Adenosine Di-Phosphate), and a phosphate group. As the rotor continues to turn the section closes and the phosphate is chemically bound to the ADP to form ATP (Adenosine Tri-Phosphate).

ATP Picture

ATP is what your body uses (especially in muscle cells) to store energy, and the process of breaking it up into ADP and phosphate is what releases that energy. More technically, the diphosphate state is at a lower energy, so when the body breaks off the extra phosphate group in ATP it releases energy which the body can then use. The rotor combines an extra phosphate group with the lower energy ADP using the cell wall's potential as the driving force. A nice picture of ATP with the three phosphate groups clearly visible is at left, and above it is a picture of ADP. Their original site with a detailed explanation of the molecule is available here.

A much more technical explanation of this entire process is available here from Prof. William Allison of UCSD. A similarly technical but more detailed description of the entire process is available here from Arizon State University's Prof. Wayne Frasch.

For a better understanding a diagram can be useful. The process was graphically modeled by Prof. Hong-Yung Wang in the following way:
ATPase Cycle Diagram

The Motor:

From that description of the function of the motor it is clear that there are two parts to the motor, the rotor section, including the portion which deals with the potential difference, called the F0 portion, and the F1 portion, in which the ADP -> ATP reaction actually occurs. The F1 portion is much better understood. In fact, we have very precise diagrams of the placement of the individual molecules and atoms of the F1 portion (available below). The F0 portion, however, has proved itself to be more difficult to understand. As a result, computer models are commonly used in studying it.

One computer simulation of the F0 portion of the motor is available on this website here. Some more complicated and detailed simulations have been constructed by other teams, although at the current time this site has the ONLY models available on the web.

This engine is common throughout the human body, and as a result it is fairly simple to extract and study the motor separately from other parts of the cell. Two excellent photographs taken with an electron microscope are readily available which clearly depict the two parts of the engine. The picture on the far right shows a model of exactly what you are seeing in these photographs.
Photo 1 Photo 2 Schematic
First Electron Microscope Picture Second Electron Microscope Picture Schematic


The Research:

In fact, Prof. Wang has done a great deal of research and work into the modeling of all the processes involved in ATPase. The structure of the F1 portion of this motor, as stated earlier, is much better understood. Prof. Wang created a model of each part; the more cartoon-like F0 model is available here, and the more detailed movie of the F1 portion in action is available here. Wang's Model of the entire structure of the motor can be seen at right, with the F0 portion above the F1 portion (flipped from the eariler pictures). Note that the actual molecular structure of the bottom portion is detailed, whereas the top is simply geometrical at this point. In fact, there is some question as to how exactly the F1 portion of the motor is formed. Its effect seems clear: a change in potential and a force on the rotor. The method through which it uses the potential to spin the rotor is not clearly understood.

Wang's Model of the Appearance of the ATPase Motor

Prof. Wolfgang Junge created an impressive animation of the entire process, clear and correct. Note his combination of (in the beginning) a detailed version of Prof. Wang's cartoony F0 model, and (as the camera moves) a more understandable version of the F1 portion of the motor. It is available here.

A New Beginning:

Recently a Japanese team (Noji et al.) undertook an experiment to prove that the F0 portion of the engine does in fact work as a rotor. They effectively tied down one end of the rotor to a slide and then attached a long protein strain in order to make the result visible to an optical microscope. The results which they recorded were more clear than even they had hoped. A schematic of Noji's experiment is below, and the video which he recorded can be found here. Notice within the video that the discrete steps of the motor can be seen; it's jumping is due to the effects of a 120 degree step. The shuffling about which does not come as a result of a nice 120 degree step is due to Brownian motion; the rotor jerks randomly back and forth as it walks forward. The cause of this stepping can be seen in the diagrams of the motor. The F1 portion is broken into 3 symmetrical pieces, each of which contains two pieces itself (labeled alpha and beta above).
Noji's Schematic

Their work proved to the scientific community that the F1 portion of this ATPase motor was a perfect nano-motor, and could be used in any number of projects. Research sprung up from this simple discovery, and there are now a number of teams working on using this motor as, for instance, a power source for nanomachines or a key piece to a microscopic pharmacy.

Some researchers at Cornell University have been working on an application for the F1 portion of the motor in molecular propulsion. Later the next year the same group successfully powered a molecular machine by attaching a tiny metallic propeller to the ATPase motor.