Lecture 3 Topic: Structure and functions of proteins.

Name. The name "protein", meaning "preeminent" or "first" is well chosen by Jons Jacob Berzelius, a Swedish chemist (1838) because the proteins play a very significant role in the structure and metabolism of the cell (G. proteios = first place).

Percentage. The proteins form about 12% of the cell contents. They are next to water as a com­ponent of the cell.

Composition. The proteins are composed of carbon, hydrogen, oxygen, nitrogen and sulphur. Certain proteins may contain phosphorus, iron or other elements also. The proteins are linear, un-branched polymers of amino acids. Twenty amino acids commonly occur in natural proteins. In a protein molecule, the amino acid units are linked together by peptide bonds

(- NH - CO) formed between the amino and the carboxyl groups of suc­cessive amino acids. The order in which amino acids occur is specific for a particular polypeptide. The protein molecules are very large and highly complex, and have very high molecular weights.

Insulin (human) has 22 and 31 amino acids in its two polypeptide chains, spinach protein ferredoxin has 97 amino acids, and the human serum albumin has 582 amino acids.

Variety. The proteins show an un­limited variety because a polypeptide may have any number of twenty amino acids present in any proportion and arranged in any sequence. Even a small polypeptide with 50 amino acids units can have 20⁵⁰ different sequences. There are 1000 to 2000 types of proteins in a bacterial cell, and over 10,000 types of proteins in the human body.

Structural Levels. Proteins have four structural levels : primary, secondary, ter­tiary and quaternary.

1. Primary Structure. The linear se­quence of amino acid units in a polypeptide chain is called the primary (1°) structure of a protein molecule. This sequence is deter­mined by the sequence of nucleotide triplets in the DNA of the cell's nucleus or nucleoid. The enzyme ribonuclease is a protein with primary structure only. So is myoglobin. A protein having a single polypeptide chain is called monomeric protein.

The work of finding out the amino acid se­quence of proteins was pioneered by the double Nobel prize winner Frederick Sanger in 1954. He worked out the amino acid sequence of bovine insulin which has 51 amino acids units.

2. Secondary Structure. A polypeptide chain is often coiled into a regular spiral, called the alpha helix, to have a 3-dimensional form. The amino acids are so placed that their side chains extend outward from the spiral. The helical structure is maintained by a series of regularly spaced intramolecular hydrogen bonds formed be­tween the carboxyl (—CO) and amino

( —NH) groups of the amino acid units in the successive turns of the spiral. The alpha coil may at places be much less regular, forming random coils. Two or more polypeptide chains may join together by intermolecular hydrogen bonds and may bend into parallel folds to form a -pleated sheet. The alpha helix, random coil and -pleated confor­mations are termed the secondary (2°) structure of proteins. Keratin of hair and myosin of muscle have helical structure, and fibroin, the protein in silk fibres produced by insects and spiders, has pleated structure. The protein lysozyme occurs in both helical and pleated forms.

3. Tertiary Structure. The helical polypeptide molecule may fold on itself and assume a complex but specific form - spherical, rod-like or any form inbetween these. These geometrical shapes are known as the tertiary (3°) structure of protein molecules. The coils and folds of the polypeptide molecule are so arranged as to hide the nonpolar amino acid chains inside and to expose the polar side chains. The tertiary structure of a protein brings distant amino acid sidechains nearer to form active sites of enzyme proteins. The tertiary struc­ture is maintained by weak bonds, such as hydrogen, ionic, disulphide* and hydrophilic-hydrophobic bonds, formed between one part of a polypeptide and another. The biological activity of a protein molecule depends largely on the specific tertiary structure. This functional form of protein is called native state. This structure is easily disrupted (denatured) by pH, temperature and chemicals, stopping the function of proteins. Tertiary structure is found in globular proteins.

Helical and pleated conformation of proteins

4. Quaternary Structure. Certain proteins consist of a bundle of two or more polypeptide chains, each having appropriate primary, secondary and tertiary structure. Such proteins have a quater­nary (4°) structure.

Quaternary structure of haemoglobin molecule

Insulin, collagen and haemoglobin have such a structure. Insulin has two polypeptide chains linked by sulphur bridges. Col­lagen has three helical polypeptides supercoiled to form a rope-like structure of great strength. Haemoglobin has four helical polypeptide chains, two  chains and two  chains. The liver protein ferritin is formed of 20 identical polypeptides. The enzyme pyruvate dehydrogenase complex has 72 polypeptides. Individual polypep­tide chains of a quaternary protein are called subunits and the active protein itself is termed multimer.

A protein having 2 or more polypeptide chains is termed oligomeric protein.