PROTEIN STRUCTURE
Proteins are very large molecules. But just how many amino acid units must be present for a substance to be a protein? There is no universally agreed-upon answer to this question. Some authorities state that a protein must have a molar mass of at least 6000 or contain about 50 amino acid residues. Smaller amino acid polymers, containing from 5 to 50 amino acid residues, are classified as polypeptides and are not proteins. In reality, there is no clearly defined lower limit to the molecular size of proteins. The distinction is made to emphasize (1) that proteins usually serve structural or enzymatic
functions, while polypeptides usually serve hormone-related functions, and (2) that the three-dimensional conformation of proteins is directly related to function, while the relationship is not so definitive with polypeptides.
In general, for a protein molecule to serve a specific biological function, it must have a closely defined overall shape. Chemists typically describe large proteins on several levels: (1) a primary structure, (2) a secondary structure, (3) a tertiary structure, and, for the most complex proteins, (4) a quaternary structure.
The primary structure of a protein is established by the number, kind, and sequence of amino acid residues composing the polypeptide chain or chains making up the molecule. The primary structure determines the alignment of side-chain characteristics, which, in turn, determines the three- dimensional shape into which the protein folds. In this sense, the amino acid sequence is of primary importance in establishing protein shape.
Determining the sequence of the amino acids in even one protein molecule was a formidable task. The amino acid sequence of beef insulin was announced in 1955 by the British biochemist Frederick Sanger (1918– ). This accomplishment required several years of effort by a team under Sanger’s direction. He was awarded the 1958 Nobel Prize in chemistry for this work. Insulin is a hormone that regulates the bloodsugar level. A deficiency of insulin leads to the condition known as diabetes. Human insulin consists of 51 amino acid units in two polypeptide chains. The two chains are connected by disulfide linkages (-S-S-) of two cysteine residues at two different sites. Insulin from other animals differs slightly by one, two, or three amino acid residues in chain A.
functions, while polypeptides usually serve hormone-related functions, and (2) that the three-dimensional conformation of proteins is directly related to function, while the relationship is not so definitive with polypeptides.
In general, for a protein molecule to serve a specific biological function, it must have a closely defined overall shape. Chemists typically describe large proteins on several levels: (1) a primary structure, (2) a secondary structure, (3) a tertiary structure, and, for the most complex proteins, (4) a quaternary structure.
The primary structure of a protein is established by the number, kind, and sequence of amino acid residues composing the polypeptide chain or chains making up the molecule. The primary structure determines the alignment of side-chain characteristics, which, in turn, determines the three- dimensional shape into which the protein folds. In this sense, the amino acid sequence is of primary importance in establishing protein shape.
Determining the sequence of the amino acids in even one protein molecule was a formidable task. The amino acid sequence of beef insulin was announced in 1955 by the British biochemist Frederick Sanger (1918– ). This accomplishment required several years of effort by a team under Sanger’s direction. He was awarded the 1958 Nobel Prize in chemistry for this work. Insulin is a hormone that regulates the bloodsugar level. A deficiency of insulin leads to the condition known as diabetes. Human insulin consists of 51 amino acid units in two polypeptide chains. The two chains are connected by disulfide linkages (-S-S-) of two cysteine residues at two different sites. Insulin from other animals differs slightly by one, two, or three amino acid residues in chain A.
The secondary structure of proteins can be characterized as a regular three-dimensional structure held together by hydrogen bonding between the oxygen of the C=O and the hydrogen H-N of the groups in the polypeptide chains:
The most common secondary structures are the alpha-helix and the beta-pleated sheet. An alpha-helix is a right-handed coil of the protein backbone, much like the coil of a spiral staircase . Each turn of the helix contains 3.6 amino acid residues, with a distance between coils of 540 pm, or 5.4 Å. The structure is stabilized by hydrogen bonds between amide N–H groups and C=O groups four residues away, with an N–H····O distance of 2.8 Å. The alpha-helix is an extremely common secondary structure, and almost all globular proteins contain many helical segments.
|
A beta-pleated sheet differs from an helix in that the peptide chain is fully extended rather than coiled and the hydrogen bonds occur between residues in adjacent chains. The neighboring chains can run either in the same direction (parallel) or in opposite directions (antiparallel), although the antiparallel arrangement is more common and energetically somewhat more favorable.
The tertiary structure of a protein refers to the distinctive and characteristic conformation, or shape, of a protein molecule. This overall three-dimensional conformation is held together by a variety of interactions between amino acid side chains. These interactions include (1) hydrogen bonding, (2) ionic bonding, and (3) disulfide bonding. Here are some examples:
|
The tertiary structure depends on the number and locations of these interactions, variables that are fixed when the primary structure is synthesized. Thus, the tertiary structure depends on the primary structure. For example, there are three locations in the insulin molecule where the primary sequence permits disulfide bonding. This specificity has an obvious bearing on the shape of insulin.
Hair is especially rich in disulfide bonds. These can be broken by certain reducing agents and restored by an oxidizing agent. This fact is the key to “cold” permanent waving of hair. Some of the disulfide bonds are broken by applying a reducing agent to the hair. The hair is then styled with the desired curls or waves. These are then permanently set by using an oxidizing agent to reestablish the disulfide bonds at different points. The two reactions involved are as follows:
Hair is especially rich in disulfide bonds. These can be broken by certain reducing agents and restored by an oxidizing agent. This fact is the key to “cold” permanent waving of hair. Some of the disulfide bonds are broken by applying a reducing agent to the hair. The hair is then styled with the desired curls or waves. These are then permanently set by using an oxidizing agent to reestablish the disulfide bonds at different points. The two reactions involved are as follows:
A fourth type of structure, called a quaternary structure, is found in some complex proteins. These proteins are made of two or more smaller protein subunits (polypeptide chains). Nonprotein components may also be present. The quaternary structure refers to the shape of the entire complex molecule and is determined by the way in which the subunits are held together by noncovalent bonds—that is, by hydrogen bonding, ionic bonding, and so on.