Levels of organization in proteins
Proteins are an important class of biological macro molecules which are the polymers of amino acids.
For a particular protein function, the presence of specific amino acids at a specific number is very important.
Four levels of structural organization of proteins.
They are: – Primary structure – Secondary structure – Tertiary structure – Quaternary structure
Primary structure of protein:
Definition: The unique liner sequence of amino acids joined by peptide bond (amide bond) that make up a protein or polypeptide chain.
Importance of Primary structure
- Higher levels of organization of Proteins are dependent on the primary structure
- Even a single amino acid change (mutation) in the linear sequence – cause disease
Eg: Sickle Cell Anemia
- In HbA (normal Hemoglobin) glutamic acid is the 6th amino acid in the beta chain. In HbS (sickle cell anemia) glutamic acid is changed to valine.
- Primary structure denotes the number and sequence of aminoacids in the peptide chain and location of disulfide bonds if present.
- The primary structure is maintained by the covalent¢ peptide bond
- Peptide bonds are not broken down by conditions¢ that denature proteins such as heating or high concentrations of urea.
Structure of insulin
- The simplest protein is Insulin. Insulin consists of 51 amino acid residues.
- It is the first protein to have its primary structure determined.
- Insulin is a protein hormone composed of two polypeptide chains: A chain (21 aminoacids) and B chain (30 aminoacids).
- A chain and B chains are linked together by two disulfide bonds. It also have an additional disulfide bond formed within the A chain.
The spatial arrangement aminoacid residues that are adjacent in the primary structure by twisting and folding of the polypeptide chain.
Common types of secondary structure: α helix, β pleated sheet, loops and turns.
Not all part of the polypeptide chain take an alpha-helix or a beta conformation (secondary structure). There are also bends, loops or turns.
Example: Carboxypeptidase shows 38 % of the amino acids forming alpha-helix and 27 % forming beta structures and around 35 % of the residues are not included in these secondary structures.
Some regions of the long chain amino acids will form alpha helices and other regions will form beta pleated sheet structure. These two types of shapes combine together and give the protein its final shape. Finally the job of the protein is determined by this shape.
- Peptide chain with its secondary structure may be further folded & twisted about itself forming 3D arrangement of a functional protein.
- Tertiary structure is the complete three dimensional structure of a polypeptide chain.
- It is a compact structure. Hydrophobic side chains held interior and hydrophilic groups are on the surface of the protein molecule.
- The function of a protein depends on its tertiary structure. If this is disrupted, it loses its activity.
The final 3 D shape is determined by a variety of bonding interactions between the “side chains” on the amino acids.
- Hydrogen bonds • Ionic Bonds • Disulphide Bridges • Hydrophobic Interactions
There are two general classes of proteins based on tertiary structure: fibrous and globular.
Fibrous proteins: Serve mainly structural roles. They have simple repeating elements of secondary structure.
Globular proteins: They have more complicated tertiary structures. They often contain several types of secondary structure in the same polypeptide chain.
The first globular protein structure to be determined: Myoglobin (using x-ray diffraction methods).
Tertiary structures may contain common patterns or motifs of secondary structures.
The complex structures of globular proteins can be analyzed by examining stable substructures called supersecondary structures motifs or folds.
Determination of tertiary structure of protein:
- X-ray crystallographic studies
- Nuclear Magnetic Resonance studies
Proteins having single polypeptide chains: Monomeric proteins
Proteins having more than one polypeptide chains: Oligomeric proteins
A multi subunit protein is also referred to as a multimer. Multimeric proteins can have from two to hundreds of subunits.
Each polypeptide chain in the oligomeric protein is called subunits or monomers.
Dimer – 2 polypeptide chains,
Tetramer – 4 polypeptide chains.
Most multimeric proteins have identical subunits or repeating groups of non identical subunits, usually in symmetric arrangements.
Protomer: structural unit of an oligomeric protein.
Subunits either function independently or may work cooperatively.
The protein lost its function when subunits dissociate.
Bonds involved: Non covalent interactions.
(For more details refer lecture notes on hemoglobin and myoglobin)