Proteins & Their Basic Structure
A. What can protein do?
DNA is often depicted as the blueprint of the cell. A blueprint is something an architect refers to in building a structure. It contains a representation of the final shape, its dimensions, whatís connected to what, and so forth. If you examine DNA, you will find none of this. The molecule has no knowledge of the cell's final shape, nor any other of the things that characterize blueprints. DNA merely lists the components that make up the proteins of a cell. But that is enough.
The weight of action, then, lies squarely on protein. Table 1 gives a synopsis of some functions performed by protein. At the top of the list is the catalysis of the chemical reactions, as emphasized in the last section. The enzyme tyrosine hydroxylase, for example, catalyzes the conversion of tyrosine to the neurotransmitter L-DOPA.
Proteins are responsible for other functions besides catalysis. They are required for the transport of a variety of compounds through membranes or, in the case of hemoglobin, the transport of oxygen in solution. Protein also plays a passive, structural role, for example in connective tissue. There are many other roles for protein, and Table 1 could have been many times as big as it is.
Table 1. Some Biological Functions of Proteins
|Binding: transport||Hemoglobin (oxygen transport)|
|Binding: defense||Immunoglobins (immune system)|
|Binding: information||Insulin (hormone) & Insulin Receptor|
|Mechanical Support||Collagen (connective tissue)|
|Mechanical Work||Actin/Myosin (muscle contraction)|
B. What are proteins?
The function of a protein is determined ultimately by its particular shape and structure. At its most basic level, the structure of a protein is simple. It has to be, otherwise DNA could not specify it. Understanding the structure of protein thus answers two profound questions:
How do proteins control the activities of a cell?
How do genes exert control over those activities?
In brief, a protein is a linear array of amino acids. If you grasp all that sentence has to say, then you've come a long way towards understanding protein. Notice the pattern in Figure 1c. A protein is a polymer of a unit repeated again and again. That unit is an amino acid. Amino acids have some parts of their structure in common, but they differ from each other in one key position, the one labelled R in the diagram.
The synthesis of proteins is the process of combining amino acids in a linear chain. The backbone of this chain is identical for all proteins. If the R groups were similarly invariable, then all proteins would be alike, and protein would be able to do only one thing, a not very interesting thing at that.
Figure 1. Protein as a polymer of alpha-amino acids. 1a. Structure of an amino acid. "R" represents side group, as shown in Figure 2. 1b. Formation of dipeptide by joining two amino acids. 1c. Polypeptide chain composed of linked amino acids. The shapes represent the different R-groups, each with its own chemical properties.
Fortunately, the R groups vary from one amino acid to the next, amongst the 20 possibilities shown in Figure 2. This listing of the twenty major amino acids is a very good list to get to know, but not to memorize. If you go into biochemistry, you'll find that they will become etched into your brain without having to memorize them, and if you don't, there's probably no need to know the structures.
R groups differ in their chemistry. Some are acidic under normal conditions, while others are basic or neutral. The charged amino acids interact strongly with water and so we call them hydrophilic. There are other R groups that interact strongly with water but are uncharged. For example, serine contains a hydroxyl group (an OH group), just like water does, and it's no surprise that serine is hydrophilic. There are also hydrophobic amino acids, like leucine, whose R-groups would tend to segregate away from water, because they interact less strongly with water than water does with itself.
There are many other properties in which the twenty amino acids differ from one another: some are bulky, some small. And so forth. Each amino acid represents a different flavor, and the structure and properties of a protein are defined by the properties and order of its amino acids: its primary structure.
There are only twenty amino acids used to synthesize proteins, which limits what proteins are possible in nature. How constricting is this limitation? Consider the number of possible dipeptides (two amino acids joined together by a peptide bond). There are 20 possible amino acids in the first position and 20 possible amino acids in the second position. That makes 202 = 400 possible dipeptides. Similarly, there are 203 = 8000 possible tripeptides. Proteins range in size from a smallish 100 amino acids to a 1000. The number of possible proteins in nature is therefore staggering!
C. Structure and basis for catalysis
Unfortunately, knowing merely that proteins are linear arrays if (alpha-amino acids doesn't tell us how they can have the varied properties required of proteins in a living cell. In particular, it doesn't explain how proteins can act as catalysts. For this we have to see the protein in three dimensions. The protein hexokinase (Figure 3), is the enzyme that begins the degradation of glucose in the liver. If you were to see this molecule, the first thing you might notice is that the enzyme has a hole just the right size for glucose to fit into. The binding of glucose to the enzyme alters the enzyme in such a way that glucose cannot escape unless the enzyme again changes shape. This normally occurs only after the reaction catalyzed by the enzyme is complete. So glucose goes in and glucose 6-phosphate goes out.
The function of hexokinase is clearly tied up in its shape. How did the protein get to this shape? We now know that the amino acids may interact with their neighbors to form coils or other structures. These local interactions lead to what is called the second ary structure of a protein. In some cases structures common to several proteins with similar functions have been identified. There are many such motifs known, and it is sometimes possible to guess the function of a protein simply by knowing its primary structure.
Amino acids may have more distant interactions with one another, giving rise to the tertiary structure of a protein, the folding of a polypeptide chain in three dimensions. For example, the hydrophobic amino acids would tend to be sequestered in the middle of the protein, away from water, just as the hydrophobic chains of soap aggregate to minimize contact with water. Charged and other hydrophilic amino acids would tend to lie outside the protein. You can see this so some extent with hexokinase (Figure 3).
It may be, however, that any way the chain may twist, there is no folding that can avoid patches of hydrophobic amino acids from appearing at the surface of the protein. What then? In some cases, further aggregation may occur between separate protein chains, so that in the end, the completely assembled protein consists of multiple chains formed by the interaction between them. Such proteins are said to have quaternary structure. An example of this is the protein hemoglobin, the oxygen-carrying protein in blood. It consists of four separate polypeptide chains that interact with each other. Separately, each subunit can bind oxygen, due in part to the oxygen-binding molecule, heme, which fits into a hole created by the tertiary structure. But the regulation of oxygen binding, essential to the functioning of hemoglobin in the body, is apparent only when four subunits aggregate together.
The positions of specific amino acids determine not only the shape of the protein but also its capacity for catalysis (Figure 4). The folding of chymotrypsin, a digestive enzyme that catalyzes the hydrolysis (breakdown) of ingested protein in the gut, creates a local region of the enzyme called the active site. The folding happens to place the 195th amino acid in the chain, serine, near a hole that has the shape of the amino acid phenylalanine. When a phenylalanine within a protein you eat finds its way into the phenylalanine-shaped hole of chymotrypsin, the amide bond adjacent to phenylalanine is positioned close enough to serine-195 that a chemical reaction takes place, breaking the amide bond. Once that occurs, the broken protein is released. The ability of chymotrypsin to do this depends upon the precise geometry of the active site. is dependent upon a serine occurring precisely at position number 195 and upon folding occurring that places serine in exactly the right position relative to the protein being digested.