Structural Organization of Proteins

Structure of proteins:

Biochemistry refers to four distinct structural levels of proteins which are listed as follows:

A) primary structure:

The primary structure of proteins refers to the linear sequence of amino acids joined together by peptide bonds during the process of protein biosynthesis (translation).Thus the primary structure of the protein is maintained by peptide linkage between the adjacent amino acid in protein .During the representation of a primary structure of protein , the N-terminal of the amino acid is always written to the left and the C-terminal is written to the right.

The amino acid sequence of a protein is encoded in DNA . Proteins are synthesized by a series of steps called transcription (the use of DNA strand to make a complementary messenger RNA strand-mRNA and translation (the m- RNA sequence is used as a template to guide the synthesis of chain of amino acids which make up the protein.) Often, post- translation modification , such as glycosylation or phosphorylation, occur which are necessary for the biological function of the protein. While the amino acid sequence makes up the primary structure of the protein, the chemical / biological properties of the protein are very much dependent on the three - dimensional or tertiary structure.

Importance of primary structure of proteins:

The different importance of primary structure of proteins are given below :

1. Primary structure gives much information about the structure and function of protein.
2. Primary structure determines the structure of other structural proteins because a change in primary structure ultimately affects the secondary , tertiary,quarternary structure of proteins.
3. Primary structure helps to study about the normal and abnormal ( mutated) proteins and helps to diagnose the different genetic disease eg: sickle cell anemia .
4. It helps for the comparison of protein structure in different species after the sequencing of amino acid.

B) Secondary Structure of protein:

The order sequence of amino acids in a protein which provides a folding conformation in that protein is called as secondary structure of protein. The folding and coiling is produced or stabilized by hydrogen bonding between amide nitrogen and carbonyl carbon of peptide chain.Theα- helix,β- bends and collagen fibers

are the different types of secondary structure of proteins.

1. α- helix: It is the right-handed spiral coil or helix which is held together by hydrogen bonding between the carbonyl group of first amino acid residue and the amide nitrogen of fourth amino acid residue in the polypeptide chain. The hydrogen bond in the alpha helix is entrachainH- bonding. The alpha helix is found in both globular and fibrous proteins. Not all the amino acid favor the formation of alpha-helix due to the steric hindrance eg; amino acid proline disturbs the formation of helix because the imino acid is geometrically comparable with the right-handed spiral of a helix. Each turn of an alpha- helix contain 3.6 amino acid residue and each turn covers a distance of 0.54nm. The diameter of each coil is 0.54nm. The axial distance of carbon atom is 0.15nm. The peptide chain serves as the backbone of alpha- helix.

1. Electrostatic repulsion and attraction between amino acid residue with charged R- group.
2. Bulkiness of adjacent alkyl group eg; Tryptophan
3. The occurrence of the proline residue.
4. The interaction between an amino acid side chain of residue.

2)β-bends/β- sheets: In beta- sheets , alpha- polypeptide backbone are folded to each other. The surface of beta- sheets appear as pleated sheets. In beta- sheets the hydrogen bonds are perpendicular to the polypeptide backbone and the H- bond may be either intrachain or interchain. Like the alpha- helix, beta- bends are also found in both fibrous and globular protein. Sometimes beta- pleated sheet can also be formed from a single polypeptide chain by folding back on itself.

Types ofβ-sheets:

There are mainly two types of beta-bends:

a) Parallelβ-sheets: It is formed when the adjacent polypeptide chain are aligned in the same direction .

b) Anti- parallelβ-sheet : In antiparallel beta-sheet,the adjacent polypeptide chains are aligned in opposing:types of beta-sheets.

3) Beta-bends( Reverse turn):

Sometimes globular protein makes a hair pin like structure called asβ- bends . Beta- bends reverse the direction of the polypeptide chain to form a complete globular shape. The bends are stabilized by the formation of H-bonds and ionic bonds.

When 3 polypeptide chain is twisted with each other or many folds back on itself forming collagen fiber, these are called collagen fibers. Usually, these are mode by glycine,Lysine, and Proline amino acid residue.Due to the compactness of this coil, the hydrogen bonds are hidden inside.

C) Tertiary Structure of Protein:

Tertiary structure refers to the complete 3- dimensional structure of the whole polypeptide chain of a given protein. This structure describes the folding and final arrangement of a domain in the polypeptides. This structure also describes how the secondary structure such as helix, sheets, bends and loops are assembled to form domain and how this domain relates the structure with each other.

The specific folding of the protein is only thermodynamically stable with a restricted range of environmental parameters such as optimum temperature and pH outside of this range ,the protein could unfold and loose its biological activities .The tertiary structure is maintained and stabilized by the interaction of the interaction contribute to the stabilization of 3D structure which is given below:

1. Hydrophobic interaction: Due to the hydrophobicity of certain amino acids they tend to locate in the interior part of the polypeptide chain where they are associated with other hydrophobic amino acids. These are not true bonds but play a great role in maintaining the structure of protein.
2. Hydrogen bond: Amino acids which contain oxygen and nitrogen in their side chain can bind to hydrogen and there is the formation of hydrogen bond.
3. Disulfide bond: This bond is formed when S-H group of two cysteine residue are linked with each other in the same polypeptide chain or between the two different polypeptide chain . These bonds are very strong so doesn't break easily but can be broken with the use of reducing agents such as Mercaptoethanol or performic acid.
4. Ionic bond or electrostatic bond: when adjacent acidic or basic amino acid interact with each other they undergoes neutralization reaction with the formation of the ionic bond.
5. Vander Waals force: In hydrophobic interaction, when the non-polar alkyl group of amino acids is held together a weak attractive force is developed which is called as Vander Waals force ,and this force is involved in the stabilization of the tertiary structure .

4) Quarternary structure of protein:

The quaternary structure is the fourth level of protein structure . The structure formed by monomer-monomer interaction in an oligomeric protein is known as oligomeric protein. Many proteins contain two or more different polypeptide chain that is held in association by the same non-covalent forces, that stabilized the tertiary structure of the protein and not- amino acid components such as minerals, lipids, carbohydrates are also involved .

Types of quaternary structure:

There are mainly two types of quaternary structure :

a) Homogenous quaternary structure: the structure which contains two or more identical; sub units eg: enzyme phosphorylase.

b) Heterogenous quaternary structure: The structure which contains two or more non-identical sub units eg: hemoglobin which contains 2α and 2β polypeptide chains.

Stability of Protein

Due to the nature of the weak interactions controlling the three-dimensional structure , proteins are very sensitive molecules. The term native state is used to describe the protein in its most stable natural conformation in situ. This native state can be disrupted by a number of external stress factors including temperature, pH, removal of water, presence of hydrophobic surfaces, presence of metal ions and high share. The loss of secondary, tertiary and quaternary structure due to exposure to a stress factor is called denaturation.

References

Cassida, L.E Jr. Industrial microbiology. New age into publishers, 1996.

I, Stever. Biochemistry. new york: Wall freeman company, 1995.

JE, Smith. Biotechnology. Sinaeur Association, 2000.

Nelson, D L and M M Cox. Lihininger Principle of Biochemistry. Fifth. Freeman publication, 2004.

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