Proteins Health Article

Definition

Proteins are linear chains of amino acids connected by chemical bonds between the carboxyl group of each amino acid and the amine group of the one following. These bonds are called peptide bonds, and chains of only a few amino acids are referred to as polypeptides rather than proteins.

Description

Proteins are all around us. Much of the body's dry weight is protein; even bones are about one-quarter protein. The animals we eat and the microbes that attack us are likewise largely protein. The leather, wool, and silk clothing that we wear are nearly pure protein. The insulin that keeps diabetics alive and the "clot-busting" enzymes that may save heart attack patients are also proteins. Proteins can even be found working at industrial sites—protein enzymes produce not only the high-fructose corn syrup that sweetens most soft drinks, but also fuel-grade ethanol (alcohol) and other gasoline additives.

Within our bodies and those of other living things, proteins serve many functions. They digest foods and turn them into energy; they move our bodies and move molecules about within our cells; they let some substances pass through cell membranes while keeping others out; they turn light into chemical energy, making both vision and photosynthesis possible; they allow cells to detect and react to hormones and toxins in their surroundings; and, as antibodies, they protect our bodies against foreign invaders. There are simply too many proteins—possibly more than 100,000—to even consider mentioning them all.

Proteins are made up of separate compounds called amino acids. It is these amino acids that our bodies actually need, not the entire protein molecule. Some amino acids are essential—they must be obtained from diet because they cannot be synthesized by humans in adequate amounts. There are nine essential amino acids. Others are nonessential, because they can be made in the body from precursors (components) of other amino acids. There are eleven nonessential amino acids.

Protein structure

Many proteins have components other than amino acids. For example, some may have sugar molecules chemically attached. Exactly which types of sugars are involved and where on the protein chain attachment occurs will vary with the specific protein. In a few cases, it may also vary among different people. The A, B, and O blood types, for example, differ in precisely which types of sugar are or are not added to a specific protein on the surface of red blood cells.

Other proteins may have fat-like (lipid) molecules chemically bonded to them. These sugar and lipid molecules are always added after synthesis of the protein's amino acid chain is complete. Such molecules can significantly affect the protein's properties.

Many other types of molecules may also be associated with proteins. Some proteins, for example, have specific metal ions associated with them. Others carry small molecules that are essential to their activity. Still others associate with nucleic acids in chromosomal or ribosomal structures.

Scientists have traditionally addressed protein structure at four levels: primary, secondary, tertiary, and quaternary. Primary structure is simply the linear sequence of amino acids in the peptide chain. It determines the protein's shape. Secondary and tertiary structure both refer to the three-dimensional shape into which a protein chain folds. The distinction is partly historical: secondary structure refers to certain highly regular arrangements of amino acids that scientists could detect as long ago as the 1950s, while tertiary structure refers to the complete three-dimensional shape. Tertiary structure determines the function of the protein. Determining a protein's tertiary structure can be difficult even today, although researchers have made major strides within the past decades.

The tertiary structure of many proteins shows a "string of beads" organization. The protein includes several compact regions known as domains, separated by short stretches in which the protein chain assumes an extended, essentially random configuration. Some scientists believe that domains were originally separate proteins that, over the course of evolution, have come together to perform their functions more efficiently.

Quaternary structure refers to the way in which protein chains—either identical or different—associate with each other. For example, a complete molecule of the oxygen-carrying protein hemoglobin includes four protein chains of two slightly different types. Simple laboratory tests usually allow scientists to determine how many chains make up a complete protein molecule.

PRIMARY PROTEIN STRUCTURE: PEPTIDE-CHAIN SYNTHESIS. Proteins are made (synthesized) in living things according to "directions" given by DNA and carried out by RNA and proteins. The synthesized protein's linear sequence of amino acids is ultimately determined by the linear sequence of DNA bases—or of base triplets known as codons—in the gene that codes for it. Each cell possesses elaborate machinery for producing proteins from these blueprints.

The first step is copying the DNA blueprint, essentially fixed within the cell nucleus, into a more mobile form. This form is messenger ribonucleic acid (mRNA), a single-stranded nucleic acid carrying essentially the same sequence of bases as the DNA gene. The mRNA is free to move into the main part of the cell, the cytoplasm, where protein synthesis takes place.

Besides mRNA, protein synthesis requires ribosomes and transfer ribonucleic acid (tRNA). Ribosomes are the actual "factories" where synthesis takes place, while tRNA molecules are the "trucks" that bring amino acids to the ribosome and ensure that they are incorporated at the right spot in the growing chain.

Ribosomes are extremely complex assemblages. They comprise almost 70 different proteins and at least three different types of RNA, all organized into two different-sized subunits. As protein synthesis begins, the previously separate subunits come together at the beginning of the mRNA chain; all three components are essential for the synthetic process.

Transfer RNA molecules are rather small, only about 80 nucleotides long. (Nucleotides are the fundamental building blocks of nucleic acids, as amino acids are of proteins.) Each type of amino acid has at least one corresponding type of tRNA (sometimes more). This correspondence is enforced by the enzymes that attach amino acids to tRNA molecules, which "recognize" both the amino acid and the tRNA type and do not act unless both are correct.

Transfer RNA molecules are not only trucks but translators. As the synthetic process adds one amino acid after another, they "read" the mRNA to determine which amino acid belongs next. They then bring the proper amino acid to the spot where synthesis is taking place, and the ribosome couples it to the growing chain. The tRNA is then released and the ribosome then moves along the mRNA to the next codon; that is, the next base triplet specifying an amino acid. The process repeats until the "stop" signal on the mRNA is reached, upon which the ribosome releases both the mRNA and the completed protein chain and its subunits separate to seek out other mRNAs.

SECONDARY STRUCTURE. The two major types of secondary structure are the alpha helix and the beta sheet, both discovered by Linus Pauling and R. B. Corey in 1951.

In an alpha helix, the backbone atoms of the peptide chain—the carboxyl carbon atom, the a-carbon atom (to which the side chain is attached), and the amino nitrogen atom—take the form of a three-dimensional spiral. The helix is held together by hydrogen bonds between each nitrogen atom and the oxygen atom of the carboxyl group belonging to the fourth amino acid up the chain.

Beta sheets feature several peptide chains lying next to each other in the same plane. The stabilizing hydrogen bonds are between nitrogen atoms on one chain and carboxyl-group oxygen atoms on the adjacent chain. Since each amino acid has its amino group hydrogen-bonded to the chain on one side and its carboxyl group to the chain on the other side, sheets can grow indefinitely.

TERTIARY STRUCTURE. Within seconds to minutes of their synthesis on ribosomes, proteins fold up into an essentially compact three-dimensional shape—their tertiary structure. Ordinary chemical forces fully determine both the steps in the folding pathway and the stability of the final shape. Some of these forces are hydrogen bonds between side chains of specific amino acids. Others involve electrical attraction between positively and negatively charged side chains. Perhaps most important, however, are what are called hydrophobic interactions—a scientific restatement of the observation that oil and water do not mix.

Some amino acid side chains are essentially oil-like (hydrophobic—literally, "water-fearing"). They accordingly stabilize tertiary structures that place them in the interior, largely surrounded by other oil-like side chains. Conversely, some side chains are charged or can form hydrogen bonds. These are hydrophilic, or "water-loving," side chains. Unless they form hydrogen or electrostatic bonds with other specific side chains, they will stabilize structures in which they are on the exterior, interacting with water.

The forces that govern a protein's tertiary structure are simple. With thousands or even tens of thousands of atoms involved, however, the interactions can be extremely complex. Today's scientists are only beginning to discover ways to predict the shape a protein will assume and the folding process it will go through to reach that shape.