By Robert Hazen, George Mason University
Determining the complete structure of a single protein can take teams of researchers years to complete. So far, no one’s learned how to predict the structure of a protein just by knowing the sequence of amino acids. That remains a great challenge. Why is that?
Variety in Proteins
The scientists who determined the structure of hemoglobin, for example, took 20 years, and they won the Nobel Prize for their effort. This effort is absolutely vital to understanding life. If one is going to understand how blood works, how oxygen is transported through the body, one has to understand the structure of hemoglobin, which takes oxygen from one part of the body to another. It’s the exact shapes of these large molecules, after all, that enable them to perform their special functions.
One might be wondering how there could be much variety in proteins when there are only 20 different amino acids to play with, only 20 different building blocks; it doesn’t sound like very many. But considering just how many different possibilities there are if we just have 12 amino acids in a row—a very small peptide, with only 12 amino acids, it is mind boggling. The first position in that peptide can have any one of the 20 amino acids, so there are 20 possible amino acids for the first position.
The second position can also have any one of the 20; so there’s 20 times 20, or 400 possibilities with 2 amino acids. Multiply times 20 again: 8,000 possibilities with 3 peptides, and on and on. Each time we add one more amino acid, we have 20 additional possibilities. With just 12 amino acids in the sequence, the number is huge; it’s 20 to the 12th power. That’s about 40 billion different peptides with just 12 amino acids, and of course, many proteins have thousands of amino acids. For all intents and purposes, the number of different protein structures is infinite.
This is a transcript from the video series The Joy of Science. Watch it now, on Wondrium.
Protein’s Folded Shape and Its Function
The importance that we attach to understanding the protein structures lies in the close relationship between a protein’s folded shape and its function in biological systems. Structural proteins (things like hair and muscles and tendons) form a variety of these supporting structures. Some of the structures are like cables, like very strong wires or ropes; others are sheet-like materials.
Let’s just think about these physical structures that are in our body for a second. We have hair, we have tendons. Just like spiderwebs, these are all made of strong, very, very rigid chains of amino acids, and so they have tremendous strength. For a given diameter of protein, the strength is generally stronger than that of steel. Some proteins, by contrast, have much smoother shapes and surfaces. For example, the cartilage which coats our joints has to have very, very smooth surfaces, and so the proteins form flat sheets; they’re folded back on each other, and have a very different function, because they have a very different form.
Modified Patterns in Biological Systems
Sometimes, in biological systems the patterns on protein structures can be modified; they can be altered, and, sometimes, very much for the worse. In some hereditary forms of arthritis, for example, the protein sheets that are supposed to be smooth have kinks in them; they have bumps, they have irregularities. Those joints wear out much, much more quickly, and consequently one can develop arthritis at a very young age.
In other cases, these variations can be quite advantageous. For example, in sheep, the hair proteins have little kinks in the protein chain, and this causes the wool of sheep to be much more tightly coiled and kinked; it forms much better insulation, and that’s why we value wool as a form of material.
The Future Looks Exciting
To conclude, wouldn’t it be easy if we just knew—for example, we have lysine, glycine, alanine, leucine and so forth, in a chain that goes on and on, and we plug that into a computer; the computer would tell us how the whole structure would fold up on itself.
Tremendous progress is being made in this direction, and it’s being done with computers. Computers have information on dozens, maybe hundreds of different protein structures, and by seeing similarities from one structure to another, one starts seeing empirical trends. This may eventually lead us to the ability to use a computer to calculate the shape of proteins. Yet, we’re still a long way from that, and that remains one of the really exciting frontiers of science right now.
Common Questions about Variation in Protein Structures and Shapes
The importance that we attach to understanding the protein structures lies in the close relationship between a protein’s folded shape and its function in biological systems.
We have hair and tendons. Just like spiderwebs, these are all made of strong, very rigid chains of amino acids, and so they have tremendous strength. For a given diameter of protein, the strength is generally stronger than that of steel.
Sometimes, in biological systems the patterns on protein structures can be modified; they can be altered, and, sometimes, very much for the worse. In some hereditary forms of arthritis, for example, the protein sheets that are supposed to be smooth have kinks in them; they have bumps, they have irregularities. Those joints wear out much, much more quickly, and consequently one can develop arthritis at a very young age.
