A protein (in Greek πρωτεϊνη = first element) is a complex, high molecular weight organic compound that consists of amino acids joined by peptide bonds. Proteins are essential to the structure and function of all living cells and viruses. Many proteins are enzymes or subunits of enzymes. Other proteins play structural or mechanical roles, such as those that form the struts and joints of the cytoskeleton. Still more functions filled by proteins include immune response and the storage and transport of various ligands. In nutrition, proteins serve as the source of amino acids for organisms that do not synthesize those amino acids natively.
Proteins are one of the classes of bio-macromolecules, alongside polysaccharides and nucleic acids, that make up the primary constituents of living things. They are amongst the most actively studied molecule in biochemistry and were discovered by Jöns Jacob Berzelius, in 1838.
Main article: Protein structure
Proteins are amino acid chains that fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native state, which is determined by its sequence of amino acids. Biochemists refer to four distinct aspects of a protein's structure:
In addition to these levels of structure, proteins may shift between several similar structures in performing their biological function. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations," and transitions between them are called conformational changes.
The primary structure is held together by covalent peptide bonds, which are made during the process of translation. The secondary structures are held together by hydrogen bonds. The tertiary structure is held together primarily by hydrophobic interactions but hydrogen bonds, ionic interactions, and disulfide bonds are usually involved too.
The process by which the higher structures form is called protein folding and is a consequence of the primary structure. Although any unique polypeptide may have more than one stable folded conformation, each conformation has its own biological activity and only one conformation is considered to be the active, or native conformation.
The two ends of the amino acid chain are referred to as the carboxy terminus (C-terminus) and the amino terminus (N-terminus) based on the nature of the free group on each extremity.
Protein Data Bank (PDB)
Main article: Protein Data Bank
The structure of proteins can be determined crystallographically or by nuclear magnetic resonance. Protein structures solved by these methods are commonly deposited in the freely accessible Protein Data Bank. Nearly 25,000 protein structures have been deposited therein, as of June 2004. This database also contains structures of nucleic acids such as DNA and RNA, as well as a few carbohydrates.
Proteins are involved in practically every function performed by a cell, including regulation of cellular functions such as signal transduction and metabolism. For example, protein catabolism requires only a few enzymes termed proteases.
Mechanisms of protein regulation
Various molecules and ions are able to bind to specific sites on proteins. These sites are called binding sites. They exhibit chemical specificity. The particle that binds is called a ligand. The strength of ligand-protein binding is a property of the binding site known as affinity.
Since proteins are involved in practically every function performed by a cell, the mechanisms for controlling these functions therefore depend on controlling protein activity. Regulation can involve a protein's shape or concentration. Some forms of regulation include:
- Allosteric modulation: When the binding of a ligand at one site on a protein affects the binding of ligand at another site.
- Covalent modulation: When the covalent modification of a protein affects the binding of a ligand or some other aspect of a the protein's function.
Proteins are generally large molecules, having molecular masses of up to 3,000,000 (the muscle protein titin has a single amino acid chain 27,000 subunits long). Such long chains of amino acids are almost universally referred to as proteins, but shorter strings of amino acids are referred to as "polypeptides," "peptides" or very rarely "oligopeptides". The dividing line is somewhat undefined, although a polypeptide may be less likely to have tertiary structure and may be more likely to act as a hormone (like insulin) rather than as an enzyme or structural element.
Proteins are generally classified as soluble, filamentous or membrane-associated (see integral membrane protein). Nearly all the biological catalysts known as enzymes are proteins. (Certain RNA sequences were shown in the late 20th century to have catalytic properties as well.) Membrane-associated exchangers and ion channels, which move their substrates from place to place but do not change them; receptors, which do not modify their substrates but may simply shift shape upon binding them; and antibodies, which appear to do nothing more than bind, all are proteins as well. The filamentous material that makes up the cytoskeleton of cells and much of the structure of animals is also protein: microtubules, actin, intermediate filaments, collagen and keratin are components of skin, hair, and cartilage. Another class are the motor proteins such as myosin, kinesin, and dynein. Muscles are composed largely of the proteins myosin and actin.
Working with proteins
Proteins can be picky about the environment in which they are found. They may only exist in their active, or native state, in a small range of pH values and under solution conditions with a minimum quantity of electrolytes, as many proteins will not remain in solution in distilled water. A protein that loses its native state is said to be denatured. Denatured proteins generally have no secondary structure other than random coil. A protein in its native state is often described as folded.
One of the more striking discoveries of the 20th century was that the native and denatured states in many proteins were interconvertible, that by careful control of solution conditions (by for example, dialyzing away a denaturing chemical), a denatured protein could be converted to native form. The issue of how proteins arrive at their native state is an important area of biochemical study, called the study of protein folding.
Through genetic engineering, researchers can alter the sequence and hence the structure, "targeting", susceptibility to regulation and other properties of a protein. The genetic sequences of different proteins may be spliced together to create "chimeric" proteins that possess properties of both. This form of tinkering represents one of the chief tools of cell and molecular biologists to change and to probe the workings of cells. Another area of protein research attempts to engineer proteins with entirely new properties or functions, a field known as protein engineering.
Protein and nutrition
In carnivores protein is one of the largest component of the diet. The metabolism of proteins by the body releases ammonia, an extremely toxic substance. It is then converted in the liver into urea, a much less toxic chemical, which is excreted in urine. Some animals convert it into uric acid instead.
Protein nutrition in humans
In terms of human nutritional needs, proteins come in two forms: complete proteins contain all eight of the amino acids (Threonine, Valine, Tryptophan, Isoleucine, Leucine, Lysine, Phenylalanine, and Methionine) that humans cannot produce themselves, while incomplete proteins lack or contain only a very small proportion of one or more. Humans' bodies can make use of all the amino acids they extract from food for synthesizing new proteins, but the inessential ones themselves need not be supplied by the diet, because our cells can make them ourselves. When protein is listed on a nutrition label it only refers to the amount of complete proteins in the food, though the food may be very strong in a subset of the essential amino acids. Animal-derived foods contain all of those amino acids, while plants are typically stronger in some acids than others. Complete proteins can be made in an all vegan diet by eating a sufficient variety of foods and by getting enough calories. It was once thought that in order to get the complete proteins vegans needed to do protein combining by getting all amino acids in the same meal (the most common example is eating beans with rice) but nutritionists now know that the benefits of protein combining can be achieved over the longer period of the day. Ovo-lacto vegetarians usually do not have this problem, since egg's white and cow's milk contain all essential amino acids. Peanuts, soy milk, nuts, seeds, green peas, Legumes, the alga spirulina and some grains are some of the richest sources of plant protein.
All eight essential amino acids must be part of one diet in order to survive and are needed in a fixed ratio. A shortage on any one of these amino acids will constrain the body's ability to make the proteins it needs to function.
Different foods contain different ratios of the essential amino acids. By mixing foods that are rich in some amino acids with foods that are rich in others, one can acquire all the needed amino acids in sufficient quantities. Omnivores typically eat a sufficient variety of foods that this is not an issue, however, vegetarians and especially vegans should be careful to eat appropriate combinations of foods (e.g. nuts and green vegetables) so as to get all the essential amino acids in sufficient quantities that the body may produce all the proteins that it needs.
Protein deficiency can lead to symptoms such as fatigue, insulin resistance, hair loss, loss of hair pigment (hair that should be black becomes reddish), loss of muscle mass (proteins repair muscle tissue), low body temperature, and hormonal irregularities. Severe protein deficiency is fatal.
Excess protein can cause problems as well, such as causing the immune system to overreact, liver dysfunction from increased toxic residues, possibly bone loss due to increased acidity in the blood, foundering (foot problems) in horses, and can also be linked to obesity.
Proteins can often figure in allergies and allergic reactions to certain foods. This is because the structure of each form of protein is slightly different, and some may trigger a response from the immune system while others are perfectly safe. Many people are allergic to casein, the protein in milk; gluten, the protein in wheat and other grains; the particular proteins found in peanuts; or those in shellfish or other seafoods. It is extremely unusual for the same person to adversely react to more than two different types of proteins.
The first mention of the word protein, which means of first rank, were from a letter sent by Jöns Jacob Berzelius to Gerhardus Johannes Mulder on 10. July 1838, where he wrote:
- «Le nom protéine que je vous propose pour l’oxyde organique de la fibrine et de l’albumine, je voulais le dériver de πρωτειοξ, parce qu’il paraît être la substance primitive ou principale de la nutrition animale.» translated as:
- "I propose to you the name 'protein' for the organic oxide of fibrin and albumin, which I have derived from [the Greek word] πρωτειοξ, because it appears to be the primitive or principle substance of animal nutrition."
Investigation of proteins and their properties had been going on since about 1800 when scientists were finding the first signs of this, at the time, unknown class of organic compounds.