Essay on the Structure of Protein (1982 Words)

Read this essay  on the Structure of Protein.

Proteins have not only a definite covalent structure but also a definite 3-dimensional structure. 3D structure is controlled primarily by the order of amino acid residues. The stability of 3D structure is due to the non-covalent bonds. The position of reactive functional groups relative to one another in an environment of controlled polarity allows proteins to bind with other molecules.

Globular Protein:

General form of the protein is globular. They are roughly spherical. X- ray crystallography studies show that globular protein is packed as tightly with amino acid residues as amino acids are packed in amino acid crystals.

Most of the side chains of amino acids are non-polar; the interior of the protein molecule is predominantly a polar. Polar amino acids are confined mainly to the exterior side of the protein.

Fibrous protein:

The major fibrous proteins are keratins, the main constituents of hair, beaks, nail and claws, scales, horn, hoove and wool, etc. Collagen of skin, cartilage and bone also are fibrous proteins. Collagen are the glycoproteins composed of glycine, proline hydroxyproline and alanine. Collagen forms a triple helix (Fig. 48.4), cross-linked to give a rigid and inextensible material. Silk and the contractile proteins tropomyosin and paramyosin are also fibrous protein.

Some proteins are neither globular nor fibrous. Myosin, a muscle protein which non- contractile system as well, is one of the largest protein known with more than 1700 amino acid residues in its polypeptide chain. It is neither fibrous nor globular structure. Histidine with its lone electron pair in the ring nitrogen often acts as an efficient acid-base catalyst.

Histidine also serves as a metal ligand in the iron containing proteins hemoglobin and cytochrome-c. Lysine is intimately involved in binding pyridoxal phosphate, lipoic acid and biotin. It is the component of the active site of certain enzymes, e.g., muscle aldolase.

The folding of polypeptide chain:

According to the folding of peptide chain the proteins acquire four structural levels (Fig. 48.5).

(1) Primary Structure:

The linear sequence of amino acid residues in the polypeptide chain is called primary structure or 1-D structure.

(2) Secondary Structure:

Regular folding pattern of contiguous parts of the polypeptide chain give a protein the secondary structure or 2D structures, e.g., a-helix, P-pleated sheet form.

(3) Tertiary Structure:

It is the 3D structure formed by the bonds between amino acid residues which are distant from each other in the polypeptide chain and the arrangement of secondary structure elements relative to one another. The term is applied generally to globular protein and rarely to fibrous proteins.

Conformation of protein includes both 2D and 3D structures.

(4) Quaternary Structure:

It is the structure resulting from the chains between separate polypeptide units of protein containing more than one subunit, e.g., enzyme phosphorylase a contains two identical subunits which alone are catalytically inactive but in a dimer form an active enzyme. Such structure is called homogeneous quaternary structure.

If the two subunits are dissimilar it is heterogeneous quaternary structure. The subunits are also called as protomers. Protein made up of more than one protomer is called oligomeric protein, e.g., hemoglobin is an oligomeric protein with heterogeneous quaternary structure consisting of 2 identical a-chain protomers and two identical (3-chain protomers (i. e., α₂ β₂).

Secondary Structure of Protein (2D):

The secondary structure of protein molecule generally is accomplished by consideration of polypeptide back bone alone, without analysis of amino acid side chain. The secondary structures are stabilized by hydrogen bonds between peptide imide and carboxyl groups of polypeptide back bone and not by bonds between -side chains. 3 classes of secondary structure are recognised,

(a) Helices, (b) Sheets and (c) Bonds.

The peptide bond, which is an imide (substituted amide) bond, has a planner structure. The electrons are delocalized in amide linkage, giving the C—N bond show considerable double bond characters.

Planner peptide bonds can be shown as

3 bonds make peptide chain, i.e., α-carbon to carboxyl carbon bond, imide nitrogen to α- carbon bond and C—N bond. Double bond of C—N bond limits rotation about it (Fig. 48.6). Due to rotations of groups around α-carbon (ψ and ɸ value) the chain assumes a helical configurations or a circle or a zig-zag structure (Fig. 48.6B).

All combinations of ɸ a ψ angles are not possible, as many lead to clashes between atoms in adjacent residues. Ramachandran worked on possible combinations of ɸ of ψ angles that do not clash and plotted on a conformation map. It is called Ramachandran plot.

α-Helix:

The protein a-helix is a right handed helix. It was demonstrated by L. Pauling and R.B. Torey in 1955. The chain rotates clockwise as one views down the helix axis at the polypeptide chain proceeding into the distance. The a-helix has 3.6 amino acid residues per turn and is stabilized by nearly straight hydrogen bonding between an imide group (—NH—) in the polypeptide chain and a carboxyl group (—CO—) at a position four residue away in the same chain (Fig. 48.7). Every —NH— and —CO— group can form a straight hydrogen bond, in this manner the a-helix is especially well stabilized.

The α-helix is characterized by the location of the atoms of the polypeptide chain; the amino acid side chains do influence the probability that a given sequence of amino acid residues will be four in an a-helix. Glycine residues do not foster a-helix as in the side chain only an ‘H’ atom is present.

The polypeptide chain is too flexible at a glycine residue. Protein can also assume value necessary for the a-helix. Both glycine and protein residue are considered to be helix breakers. Glutamic acid, leucine, Methionine, phenylalanine, etc., occur very frequently in a-helices and are considered to be a-helix promoting residues. Other features of a-helix are:

(a) Overlapping of repeating units after 18 amino acid residues, i.e., after, 5 turns.

(b) Pitch (centre to centre) per turn = 5.4 A.

(c) Pitch (rim to rim) of each turn = 5.1 A.

(d) Rise per residue = 1.5 A.

β-pleated Sheets:

The β-pleated sheet structure in protein is not exactly in the same plane. The sheets are pleated (Fig. 48.8). The atoms lie in folded plane, and the side chains of succeeding residues along the polypeptide chain protrude alternately above and below the general plane of the structure.

The β-pleated sheet structures, like the α-helix, allow the maximum amount of hydrogen bonding between polypeptide back bone inside and carboxyl groups, and the H-bonds formed are straight enough to be stable. The β-pleated sheets seen in protein structures are not only pleated but also slightly twisted.

α-helix and P-pleated sheet structures are found in both globular and fibrous proteins. The wide and frequent occurrence of the a-helix and p-pleated sheet structures appears to be due to the combination of sterically favoured disposition of the polypeptide chain and favourable hydrogen bonding.

α-keratin and paramyosin are examples of fibrous proteins that have a-helix structures. Parallel P-pleated sheets and antiparallel p-pleated sheets form the structures of the fibrous proteins stretches of polypeptide chain entirely folded into the secondary structures. In globular proteins the a-helical and p-pleated structures are smaller than those of fibrous proteins.

Reverse Bending:

Reverse turn or reverse bending occurs at the surface of protein in globular protein.

Super secondary structure is presented by some fibrous proteins like collagen. The amino acid composition of collagen is unusual being composed of 25% glycine and 25% proline and hydroxyproline. Because of high glycine and proline contain no α-helic occurs.

Tertiary Structures of Protein (3D Structure):

The next level after secondary structure is tertiary structure, which describes the conformation of the entire protein. The secondary structure is stabilized primarily by hydrogen bonds between atoms that form the peptide bonds of the backbone. The tertiary structure is stabilized by an array of non-covalent bonds between the diverse side chains of the protein. The secondary structure is limited to the small number of conformations but tertiary structure is virtually unlimited.

The detailed tertiary structure of a protein is usually determined using X-ray crystallography technique. Most proteins can be categorized on the basis of their overall conformations being either fibrous (elongated shape) or globular (compact shape).

Myoglobin:

The first globular protein whose tertiary structure was determined. The polypeptide chains of globular proteins are folded and twisted into complex shapes. Distant points on the linear sequence of amino acids are brought next to each other and linked by various types of bonds. John Kendrew et al in 1957 produced the 3D structure of myoglobin. Myoglobin is present in muscle tissue as a storage site for oxygen.

The oxygen molecule is bound to an iron atom in the centre of a heme group. Heme is the prosthetic group, i.e., a part of protein not composed of amino acids. The heme of myoglobin gives most muscle tissue a red colour. Myoglobin is a globular protein the polypeptide chain was folded back on itself in a complex arrangement. Myoglobin is composed of 5-rodlike stretches of a α-helix ranging from 7-24 amino acids. 75% of the 153 amino acids in the polypeptide chain are in the a-helical conformation. No, β-pleated sheet is present. (Fig. 48.9).

The 3D structure reveals that heme is present within a pocket of hydrophobic side chains that promotes the binding of oxygen without the oxidation of iron atom. No disulphide bond is present in myoglobin. Tertiary structure is held together purely by non-covalent bonds between side chains within proteins, i.e., hydrogen bonds, ionic bonds and hydrophobic interactions (Fig. 48.10).

Trios phosphate isomerase (enzyme) consists of β-pleated sheets largely and some α-helices.

There are various types of non-covalent bonds stabilizing tertiary protein structure, e.g., ionic bonds due to electrostatic interaction, hydrogen bonds between heteroatoms of side chains and between side chain and polypeptide backbone, hydrophobic interaction between non-polar side chains and disulphide bonds (Fig. 48.10).

Sub-structure of Globular Protein Molecules:

Aspects of folding of polypeptide chain in globular protein other than non-polar interior of the molecule are:

(a) Content of α-helix and β-pleated sheets varies widely from protein to protein. Myoglobin has α-helix content where as proteinase α-chymotrypsin has β-sheet structures. Triose phosphate isomerase and lactate dehydrogenease have both β-pleated sheets and α-helices. In these molecules the folding is such that α-helices and β-pleated sheets alternate along the chain.

(b) The conformation has both carboxyl and amino terminus free, i.e., if they are stretched out a linear chain would result. Polypeptide chain is not rolled up like a ball or string; but the course is from one surface of the molecule to another where it reverses its course.

(c) Useful general concept of globular protein structure is that of domain. Statistical tests that analyse the density of atom population around each amino residue in the 3D structure sometimes detect domains not apparent by viewing the protein structure model. Often, the course of the, polypeptide chain leaves one domain for a second and, after forming the second domain, returns to the first, making two polypeptide connections between the two domains. Most recognized domains have 100-200 amino acid residues, though both larger and smaller domains have been identified.

Domains have structural and evolutionary significance. An active site of an enzyme is the localized region of the molecule at which the enzyme bonds and acts on its substrate. Active sites are formed on the junction of 2 or more domains of the enzyme protein.

Domains have been postulated to facilitate the evolution of protein by providing preformed sequences of amino acids that will assume a stable conformation and provide a specific function.

The enzyme phosphofructokinase is an example of gene duplication. The phosphofructokinase of some bacteria and mammals are homogeneous tetramers, but mammalian enzyme is twice the size of bacterial enzyme. The two halves of the mammalian enzyme appear to be related super domains.

Bacterial and mammalian enzymes have the same number of active sites, i.e., four per tetramer.