No matter how small a protein molecule is, it is always composed of thousands of atoms that are bound to one another through a combination of covalent and noncovalent bonds. Biologists are able to perceive these extraordinarily complicated systems thanks to a variety of graphic and computer-based three-dimensional representations. On the student resource website that corresponds to this book, a number of different computer-generated images of selected proteins are displayed on the screen in a rotating fashion. According to the findings of experts, the structure of a protein can be broken down into four separate organizational levels. The configuration of the amino acids is the primary structural component. Proteins have secondary structures that are made up of stretches of polypeptide chains that are folded into helices and sheets. These structures are called secondary protein structures. The entire structure is referred to as the quaternary structure when a protein molecule is created as a complex of many polypeptide chains. On the other hand, the complete three-dimensional organization of a polypeptide chain is sometimes referred to as the tertiary structure.

Research on the conformation, function, and evolutionary history of proteins has also made obvious the vital significance of an organizational unit that is different from these four. The protein domain is a substructure that can fold into a compact and stable form on its own without the assistance of the rest of the protein. It is formed by any continuous polypeptide chain that is long enough. A domain is a type of protein that functions as a building block for the assembly of several larger proteins. In general, a domain will have anywhere from 40 to 350 amino acids.

The smallest protein molecules each only have a single domain, whereas larger proteins may contain several dozen domains, all of which are joined to one another by relatively short polypeptide chains that have a slightly disordered structure and can function as flexible hinges.

Some calculations suggest that less than one in a billion of this enormous collection of potential polypeptide chains would assume a stable three-dimensional structure. This is a significant percentage of the collection. Nevertheless, the vast majority of proteins found in cells do assume distinct conformations that are stable over time. How in the world is that even a possibility? The answer lies in the process of natural selection. There is a low probability that a protein with unpredictable structural variability and biochemical activity can contribute to the survival of a cell. As a result, these proteins would have been eliminated by natural selection as a result of the extremely drawn-out process of trial and error that underpins the process of biological evolution.

Since evolution has selected for protein function in living creatures, the majority of modern proteins have amino acid sequences that are designed in such a way that only a single conformation can be stable. In addition, the chemical properties of this conformation have been fine-tuned to a specific degree in order to facilitate the protein's performance of a particular catalytic or structural function within the cell. A change of even a few atoms in a single amino acid can sometimes cause the structure of the entire molecule to be badly disrupted, which results in the loss of all function. This is because proteins are so carefully constructed.

It is possible for the structure of a protein to shift over the course of evolution, allowing it to perform new functions after it has reached a stable conformation that possesses desirable properties. This process has been significantly sped up thanks to genetic mechanisms that occasionally duplicate genes and make it possible for a single gene copy to evolve on its own to carry out a new function. As a result of the frequency with which this category of occurrence has occurred in the past, many modern proteins can be arranged into protein families. Members of a given protein family share three-dimensional conformations and amino acid sequences that are similar to one another.

Take, for example, the serine proteases, which are a large family of protein-cleaving enzymes that belong to the proteolytic category. In addition to the digestive enzymes chymotrypsin, trypsin, and elastase, this group of enzymes also include a number of proteases that are necessary for the coagulation of blood. It is possible to compare and verify that some of the amino acid sequences of any two of these enzymes that contain proteases share commonalities with one another. Even more striking is the similarity of their three-dimensional conformations, which is due to the fact that the majority of the intricate turns and twists in their polypeptide chains, each of which is several hundred amino acids long, are almost identical. Each of these polypeptide chains is also known as a polypeptide chain. In spite of this, each of the multiple serine proteases has its own distinct set of enzymatic activities, which include cleaving various proteins as well as the peptide bonds that are formed between different types of amino acids. As a result, each one is responsible for a unique function within the body.

It's not uncommon for large protein families to have members that participate in a wide variety of activities. There is no shadow of a doubt that some of the variations in amino acid sequences that distinguish members of a family were selected during the course of evolution because they led to advantageous changes in biological activity. These modifications were responsible for providing the various members of the family with the distinct functional characteristics they have today. However, the vast majority of other amino acid substitutions are essentially "neutral," meaning that they have no discernible effect on the fundamental make-up of the protein or its ability to carry out its functions. Due to the fact that mutation is a chance process, there must have been a significant number of mutations that were deleterious and had a negative impact on the three-dimensional structure of these proteins. Such defective proteins would have been lost when the individual creatures that produced them became sufficiently disadvantaged to be eliminated by natural selection.

Protein families are easily identified when the genome of an organism is sequenced. For instance, the determination of the DNA sequence for the entire human genome has revealed that there are approximately 21,000 protein-coding genes in our bodies.

As was said before, the vast majority of proteins are composed of a number of protein domains. These protein domains allow for the individual folding of diverse polypeptide chain segments into more compact structures. The DNA sequences that code for each domain are assumed to have joined together by chance, resulting in the formation of a new gene, which led to the development of these multidomain proteins. In the course of evolution, a mechanism known as "domain shuffling" has caused many large proteins to evolve by causing previously existing domains to combine in innovative ways to form new combinations. It is well known that a significant number of the functional regions of proteins that are responsible for interactions with small molecules are located at the juxtaposition of domains. It is at these locations that novel binding surfaces are frequently generated.

Protein modules are a word that is used to define a group of protein domains that have been exceptionally mobile all throughout the course of evolution. It would appear that these spheres have architectures that are extremely flexible.

Each of the exhibited domains possesses a stable core structure that is composed of strands of sheets. From these sheets, less organized loops of polypeptide chain extend into the center of the domain. The immunoglobulin fold, which is the basis for antibody molecules, is the best illustration of how the loops can be ideally positioned to give binding sites for other molecules. This fold is also known as the immunoglobulin heavy chain variable region. These sheet-based domains may have been effective in their evolution because they make it straightforward to produce novel ligand binding sites while only requiring minimal alterations to their protruding loops. This feature may have contributed to their success.