L7: Protein structure, folding & misfolding Flashcards
What are the orders of protein structure?
There are four orders of protein structures:
1) Primary structure of Proteins
2) Secondary structure of Proteins
3) Tertiary structure of Proteins
4) Quaternary structure of Proteins
Primary structure of the protein
Referred to the number, type, and sequence of amino acids in the polypeptide chain.
Any change in one of the amino acids in the polypeptide chain produces a physiological defect.
The main bond in this structure is the peptide bond.
The free -NH2 group of the 1st amino acid is called as N-terminal end and the free - COOH end of the last amino acid is called as C-terminal end.
What is the secondary structure of proteins?
The polypeptide chain will be folded to give a specific shape form which may be:
a) α-Helix
b) β-pleated Sheets
c) Supersecondary structures(motifs)
α-Helix
The polypeptide chain is twisted to a right-handed coiled helix.
each turn contains 3.6 amino acids, which is a common secondary structure in globular proteins.
The formation of the α-helix is spontaneous and is stabilized by Hydrogen bonds between carbonyl Oxygen of peptide bond and hydrogen of NH of the next 4th peptide bonds in the chain.
β-pleated Sheets
Formed when hydrogen bonds are formed between two or more adjacent polypeptide chains.
The hydrogen bonds are inter-chain.
It is pleated due to the angles of bonds.
Super secondary structures (motifs)
Combinations of α-helix and β-sheets to form a specific shape.
It gives protein a specific structure feature to enable a particular function.
EX: Helix-turn-helix (HTH)
Two α helices are joined by a short strand of amino acids.
Is a major structural motif capable of binding DNA.
The tertiary structure of proteins
Secondary structures are arranged to form a final functional 3D structure called domain.
It occurs due to interaction between side chains (R) of the amino acids.
domain.
There are forces controlling tertiary protein structure.
What are the forces controlling the tertiary structure of proteins?
Hydrogen bond: Between polar side chains of amino acids.
Hydrophobic forces: Between the non-polar (R) groups of the amino acids
Electrostatic forces(ionic bonds, salt bridges): Between oppositely charged (R) groups of amino acids
Disulfide bonds: Between sulfur amino acids (cysteine)
Quaternary structure of the protein
Special arrangement of more than one polypeptide chain (subunits = monomers).
The bonds: Non-covalent (hydrogen or ionic bonds)
This high level of organization is essential for the activity of some proteins like hemoglobin, enzymes.
What are the examples of oligomeric proteins (quaternary structure of proteins)?
-Creatine kinase (CK) enzyme is a dimer.
- Haemoglobin and lactate dehydrogenase (LDH) enzymes are tetramers.
What is the definition of protein folding?
It is a physical and dynamic process by which a string of amino acids interacts with itself to form a stable three-dimensional (3D) structure during the production of the protein within the cell.
What is the importance of protein folding?
1) Production of protein structures that can perform specific functions in the cell.
2) Prevent non-specific interaction of the protein with other proteins (prevent protein aggregation).
What is the mechanism of protein folding?
Occurs spontaneously, but there is a class of specialized proteins; chaperones, whose function is to assist in this process.
What are the causes of protein misfolding?
1-Spontaneous
2-Mutation in a particular gene, which then produces an altered protein.
3-Some proteins after abnormal proteolytic cleavage can take on a
unique conformational state that leads to the formation of long fibrillar protein assemblies consisting of β pleated sheets (its accumulation →Amyloidosis).
What are the effects of protein misfolding?
There is a deposition of misfolded proteins as insoluble aggregates within the cell.
