Protein Quaternary Structure Quiz

Quaternary Structure

• Quaternary structure is the spatial arrangement of two or more polypeptide chains (subunits) forming a complex.
• Each subunit has its own primary, secondary, and tertiary structure.
• Subunits can be identical (homo-oligomers) or different (hetero-oligomers).
• Subunits are linked by non-covalent interactions (hydrogen bonds, hydrophobic and electrostatic interactions).
• Some subunits perform catalytic functions, while others are involved in recognition and regulation.
• Changes in spatial arrangement of subunits alter the molecule's properties, impacting intracellular processes.

Hemoglobin

• Hemoglobin is an example of a quaternary protein with four subunits and four hemes, each represented by a different color.

Denaturation and Renaturation

• Denaturation disrupts protein conformation due to chemical or physical agents (high temperature, acids, bases, detergents, radiation).
• Denaturation destroys quaternary, tertiary, and secondary structures, but not the primary structure.
• Denaturation can be reversible or irreversible.
• Reversible denaturation allows the molecule to regain its native conformation (renaturation) after removing the denaturing agent.
• Cells maintain protein conformation and assist in polypeptide chain folding.

Folding of Newly Synthesized Polypeptide Chains

• Special proteins facilitate the folding process, including:
  • Protein disulfide isomerases: catalyze disulfide bond rearrangement to achieve the correct conformation.
  • Prolyl cis-trans isomerases: catalyze the cis/trans conversion of X-Pro bonds, enhancing folding efficiency.
  • Chaperones: assist in protein folding and prevent aggregation.

Protein Disulfide Isomerase (PDI)

• PDI contains an active site with two cysteine sulfhydryl groups (-SH).
• One ionized form (-S-) interacts with a disulfide bridge (S-S) in proteins, forming a disulfide-linked enzyme-substrate complex.
• The complex allows disulfide bridges to rearrange until the most stable conformation is achieved, releasing the enzyme.

Peptidyl Prolyl cis-trans Isomerases (PPIase) (Cyclophilins)

• Some proteins contain a cis X-Pro bond in their native structure.
• PPIase catalyzes cis/trans conversion of X-Pro bonds, increasing the folding efficiency.
• Inhibition of cyclophilins by cyclosporins and FK506 leads to immunosuppression, used in organ transplantation to prevent rejection.

Diseases Resulting from Disordered Protein Conformation

• Mutant proteins aggregate and form non-functional, insoluble aggregates, causing disease.
• Alzheimer's disease: amyloid aggregates form in the brain.
• Prion disease: a mutant protein converts α-helix to β-helix, leading to insolubility and resistance to proteases.
• Huntington's disease: genetic HTT mutation causes abnormal huntingtin protein folding, disrupting neuronal function and leading to neuronal death.

Sickle Cell Anemia

• Replacement of polar glutamate with hydrophobic valine in HbS changes conformation and physicochemical properties, facilitating polymerization and precipitation of HbS.
• This precipitation leads to hemolysis of erythrocytes (red blood cells), causing anemia.

Cystic Fibrosis (CF)

• CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, affecting chloride and sodium ion transport across epithelial cell membranes.
• Mutations lead to thick mucus buildup, respiratory failure, and other systemic obstructions and abnormalities.
• The ΔF508 mutation, the most common CF mutation, leads to abnormal CFTR protein synthesis and degradation.
• CFTR deficiency results in decreased chloride ion permeability, causing dehydrated airway mucus and impaired airway defense mechanisms.

2,3-Bisphosphoglycerate (2,3-BPG) as a Regulator of Hemoglobin

• 2,3-BPG binds to HbA in the gap between subunits, decreasing its affinity for O2.
• This facilitates oxygen delivery to tissues.
• Fetal HbF (fetal hemoglobin) has lower affinity for 2,3-BPG, allowing it to more readily bind O2 released from maternal HbA.

Involvement of Ascorbic Acid (Vitamin C) in Collagen Maturation

• Scurvy arises from vitamin C deficiency, affecting collagen maturation.
• Vitamin C is a cofactor for prolylhydroxylase and lysylhydroxylase enzymes, which hydroxylate proline and lysine, respectively.
• Hydroxylation stabilizes collagen fibers, preventing scurvy.

Test your knowledge on the quaternary structure of proteins, focusing on hemoglobin and the concepts of denaturation and renaturation. Understand the roles of subunits, their interactions, and how structural changes affect protein function.