Eavesdropping on Proteins' Conversations

Rebecca Whelan
Department of Chemistry
Stanford University
March 2002

I am interested in finding out how proteins communicate with each other. I do this by gently attaching proteins to one side of a thin layer of gold and bouncing light off the other side. By watching changes in the reflected light as different proteins are presented to the attached proteins, I can see which proteins interact, how fast they interact, and how strongly they interact. Because of the importance of proteins to health, these studies can reveal which drugs might be effective in treating disease, or unravel questions about how proteins function in the body.

Proteins are one of the building blocks of all living things. They are vital to everything an organism does, from moving, to thinking, to digesting food. I am interested in one particular activity of proteins, which is communicating with each other. I use a technique that, like eavesdropping, enables me to hear the proteins' conversations without interrupting them. The technique relies on the fact that not all proteins are interested in each other. For their biological function, proteins have developed to recognize some proteins while completely ignoring others. Often, recognition is followed by some change in the protein's shape, which enables it to do a different job, such as make a needed material or transmit a signal from one part of its environment to another.

The protein I am currently examining is found in the heart and is responsible for the adrenaline rush. If you get into a life-threatening situation, this protein will respond to the flood of adrenaline in your system and prepare your body to fight or to flee. The protein is called a receptor because it receives a signal from adrenaline. There are many different kinds of receptors, which receive signals from different things, and as a class of proteins they are vital to the normal function of an organism. Receptors have the interesting task of communicating messages across the cell membrane, the thin skin of the cell that allows only some things to pass through. The membrane keeps the cell's contents in, while keeping the rest of the world out. However, the cell still needs a way to selectively receive information from the world outside, and that is the function of a receptor. Important messages, carried by traveling chemicals, reach the cell membrane, where they pass their message to the receptor in the membrane. By changing its shape, the receptor conveys the message to the cell's interior where it communicates with a different protein that can move around the cell and cause the cell to respond appropriately to the message from the outside. In the case of these adrenaline-sensitive receptors in the heart, the receptor interacts with adrenaline from the outside and conveys the message to another protein on the inside. When many heart cells receive this message at the same time, the heart begins to beat faster, readying the body for the "fight-or-flight" response. Obviously, if the receptor doesn't do its job properly, the heart would not have the right response to the stimulus.

To eavesdrop on the proteins, I must let them function normally. This means that rather than handling the proteins directly, I observe them indirectly. I stick one protein to a thin piece of gold. In doing so, I try not to alter the protein, since I want it to be as natural as possible. I then bounce light off the backside of the gold. The gold is so thin that some light penetrates to the other side, where it can see any proteins attached to the gold on the front. The proteins absorb light, so the reflected light is less intense than the original light. As more proteins are added to the layer on top of the gold, the reflected light becomes dimmer. I then introduce different proteins to the environment above the fixed proteins. If they have anything to say to each other, they'll bind together, making the protein layer thicker and the light dimmer.

There are two motivations for the research I do. The first is the fundamental understanding of how proteins work. Proteins are involved in many complex relationships, making them an exciting challenge for scientists. The second motivation is the role of proteins is disease. When proteins go haywire, disease is the inevitable result. In fact, over 50% of therapeutic drugs on the market or in development help receptor proteins to function smoothly. My experiments reveal the complicated conversations among proteins which maintain health, or cause its deterioration.