4. PROTEIN STRUCTURE
Protein is a polymer of amino acids. The amino acids are ligated by peptide bond during translation. Protein is folded, three-dimensional structure and amino acids in a polypeptide chain or protein are called a residue. By convention, a chain of an amino acid having less than 30 amino acid is known as peptide and more than 100 amino acids in a chain are known as a polypeptide. The oligopeptide refers to a chain of a protein having 30-100 amino acids.
4.1. Primary structure
It is a linear chain of polypeptide or protein. During translation, it is formed by covalent or peptide bonds. One end of a polypeptide is called C-terminal or carboxy-terminal while another end is called amino-terminal (N terminal). During translation, polypeptide chain grow in N terminal to C-terminal. The amino acid sequence of the protein is unique.
4.2. Secondary structure
Secondary structure is formed because of hydrogen bonding between the alpha NH2 group and alpha carboxylic group. Based on the nature of hydrogen bonding (whether intramolecular or intermolecular), Pauling and Corey (1951) identified two regular types of secondary structure in proteins: alpha helix ( -helix) and beta pleated sheet (-pleated sheet). These secondary structures have regular geometry and the specific value of and angle.
4.2.1. Types of secondary structure
Helical structure: It is formed when a polypeptide chain is twisted in a manner that each of its C2 atoms assumes same bond angle. Helix is a coiled structure.
The helix is a coiled structure. It is not linear like the primary structure of the protein. Pitch is a feature of a helix. Pitch is defined as a vertical rise of helix per turn. With x-ray diffraction studies, Pauling and Corey (1951) found that a polypeptide chain with planar peptide bonds can form a right-handed helical structure by simple twists about the -carbon-to-nitrogen and the -carbon-to-carboxyl carbon bonds. The helix is so named because of the mobility of a-carbon atoms.
The -helix is stabilized by hydrogen bonds between the NH and CO groups of polypeptide’s main chain. The CO group of each amino acid is hydrogen-bonded to the NH group of the amino acid that is situated four residues ahead in the linear sequence. Thus, all the main chain CO and NH groups participate in hydrogen bonding.
There are 3.6 amino acid residues per turn of the helix. The pitch is 5.4 A° for the alpha helix. For a polypeptide made from L--amino acid residues, the a-helix is right handed with torsion angles –57° and –47°. (An -helix of D--amino acid residues are the mirror image of that made from L-amino acid residues: It is left-handed with conformation angles 57°, 47°, and n-3.6. The pitch is the same for both the L-amino acid and D-amino acid).
Many globular proteins contain short regions of such -helices, and the transmembrane portion of a protein is usually -helices. In a helix, R group is projected outside because R group is bulkier so not present inside the helix.
Keratin and collagen are almost entirely alpha-helical in structure. The charged amino acid destabilizes the -helical structure and beta sheet and hydrophobic side chain are compatible with the formation of alpha helices and beta pleated sheet.
In an aqueous environment, an isolated -helix is usually not stable on its own. The basic structural unit of -keratin usually consists of three right-handed helical polypeptides in a left-handed coil that is stabilized by cross-linking disulfide bond.
188.8.131.52. Amino acids affecting an a-helical structure
- A prolyl residue has its a-N atom in a rigid ring system and cannot participate in a helical structure. Proline is called as helix breaker and creates a sharp bend in the helix.
- Along repeat of aspartyl and/or glutamyl residues can destabilize a-helical structure because the negatively-charged side chains repel one another (electrostatic repulsion), and the forces of repulsion are greater than those of hydrogen bonding.
- A long sequence of isoleucyl residues disrupts helix formation, because of steric hindrance imposed by their bulky R groups.
- Glycine, with a small hydrogen atom as a R group, is another destabilizer. The lack of a side chain on glycine allows for a great degree of rotation about the amino acid’s a-carbon. Thus conformations other than a helical bond angle are possible for glycine which destabilizes the helix.
4.2.2. sheet :
sheet is formed by hydrogen bonding, between the alpha carboxylic (CO) group of an amino acid with the alpha amino group (–NH) is an adjacent amino acid. It exists in antiparallel and parallel form. The antiparallel sheet is more stable. Sheets are common structural motifs in proteins. In globular proteins, they consist of from two to as many as twenty-two polypeptide strands. In -sheet hydrogen bonds are more or less one. In antiparallel -sheet hydrogen bonds are more than one and in parallel, it is less than one. Parallel and antiparallel -sheets are connected by loops.
The energetically preferred dihedral angles , are –135° and 135° respectively for sheet. However, the and angles are –140° and 135° for antiparallel Sheet and - 120° and 115° for a parallel sheet.
Globular proteins consist of an average, ~31% a helix and ~28% b sheet. The remaining polypeptide segments of protein are said to have a coil or loop conformation.
Silk fibroin is one example of a protein that has the antiparallel pleated sheet structure. It is a member of a class of fibrillar proteins called -keratin.
4.2.3. Turns :
Turns are secondary structure. They are the reversal in nature i.e. they reverse the direction of the polypeptide chain. In turn, three amino acids participate. Turn is stabilized by hydrogen bonding between the CO of residue ‘n’ and the NH of residue n + 3. Proline amino acid usually presents in turn at position number two.
The only helix can form turn, proline amino acid is sometimes known as “helix breakers”. Because they disrupt the regularity of the helical backbone conformation.
Types of turn
Basically turn are of two types designated as I and II. Type I turn to contain all residues in position n to n + 3. In type, I turn proline is present at position number two and the 3rd position is acquired by any amino acid.
Type II turn to contain a proline at a similar position to type I turn, but the third amino acid in type II turn is Glycine.
- Turn helps to form secondary structure and provide stability to protein, maintain its structure.
- Some aromatic amino acids that participate in helix formation are tryptophan, tyrosine and phenylalanine. The Methionine, Glutamate, Leucine and alanine also has a strong tendency to form a helix. Amino acids that form b sheet includes valine, isoleucine, and proline. Among these amino acids, methionine has the highest tendency to form a helix and valine has the highest tendency to form sheet. Minimum seven amino acids are required to form helix and six amino acids are required to form sheet.
4.3. Super-secondary structure
They are also called as a motif, it is a folding pattern involving two or more elements of secondary structure. Motif provides a function to the domain. They are of different types simplest among them with specific function consists of two alpha-helices joined by a loop region.
Examples of the motif are :
4.3.1. DNA binding motif:–
A motif specific for calcium bending and is present in parvalbumin, calmodulin, troponin c, and the proteins that bind calcium and thereby regulate cellular activities.
4.4. The tertiary structure of protein -
The tertiary structure of a protein is a three-dimensional structure of a protein. Tertiary structure is formed during protein folding. Protein folding involves the interaction of diverse R group (side chain) of amino acids. Various forces are involved in the formation of tertiary structure.
1. Hydrogen bonding
2. Disulphide bond
3. Electrostatic or Ionic bond
4. Hydrophobic bonding
The protein can be classified broadly based upon the tertiary structure.
(A) Globular proteins have a core of hydrophobic amino acid residue and water exposed, polar, charged hydrophilic residue on the surface. This arrangement makes protein soluble in water and stable in conformation. The disulphide bond increases the stability of a protein. The protein folding process is achieved with help of chaperons
4.4.1. Importance of tertiary structure
Protein-specific function depends on the tertiary structure. If this is disrupted, the protein is said to be denatured and the show lost its activity. eg: Denature enzymes loss its catalytic power with denatured antibodies can no longer bind with antigen. A mutation in the DNA may alter the amino acid in protein which resulted in improper folding. Misfolding protein fail to perform its function.
4.4.2. Some of the examples include:
Cystic fibrosis is caused because of failure of the mutant CFTR protein to its target place in the plasma membrane.
Diabetes is caused by improper folding of mutant versions of V2 the vasopressin (ADH) receptor and aquaporin.
Hypercholesterolemia is caused by the failure of mutant low-density lipoprotein receptors to reach the plasma membrane.
Osteogenesis imperfecta is caused by a failure of mutant type one collagen molecules to assemble correctly.
Mutant protein form inclusion bodies that are the aggregation of the insoluble protein caused by nonfunctional deposits.
4.5. Quaternary structure :
Quaternary structure is formed by more than one polypeptide. A protein with multiple polypeptide chains is multimeric in nature. Multimeric protein exhibit quaternary structure.
One Subunit Monomer
Two Subunit Dimer
Three Subunit Trimer
Four Subunit Tetramer
More than four–Multimers Changes in conformation within individual subunits can cause a change in quaternary structure.
- Book COVER AND ABOUT US
- CHEMICAL BONDING
- AMINO ACIDS
- PROTEIN STRUCTURE
- RAMACHANDRAN PLOT
- PROTEIN STABILITY
- KINETIC ANALYSIS
- REGULATION OF GLYCOLYSIS
- TRICARBOXYLIC ACID CYCLE (TCA CYCLE)
- REGULATION OF THE CITRIC ACID CYCLE
- GLYOXYLATE CYCLE OR KREBS KORNBERG CYCLE
- ELECTRON-TRANSPORT CHAIN
- MECHANISMS OF OXIDATIVE PHOSPHORYLATION
- PENTOSE PHOSPHATE PATHWAY
- LIPID METABOLISM
- FATTY ACID OXIDATION
- DNA STRUCTURE
- NUCLEOTIDE BIOSYNTHESIS