M03.04.05 Protein Folding and Subunit Assembly

Protein folding is a crucial process that determines the functionality of proteins within biological systems. As proteins emerge from ribosomes, they undergo a series of conformational changes that are essential for their biological activity. This process can be categorized into four distinct levels of protein structure: primary, secondary, tertiary, and quaternary.

Levels of Protein Structure

1. Primary Structure

• Definition: The sequence of amino acids specified by the gene.
• Significance: The primary structure dictates the overall shape and function of the protein.

2. Secondary Structure

• Definition: The folding of the amino acid chain into stable structures.
• Common Forms:
  • α-Helix: A coiled structure stabilized by hydrogen bonds.
  • β-Pleated Sheet: A zigzag structure formed by hydrogen bonding between adjacent chains.
• Characteristics: A single protein may contain both α-helices and β-pleated sheets. Some proteins, such as collagen, have unique secondary structures without these common forms.

3. Tertiary Structure

• Definition: The overall three-dimensional shape of a protein formed by the arrangement of secondary structures.
• Features:
  • Domains: Specific functional regions within the protein.
  • Overall Shape: Can be globular or fibrous.
• Stabilization: Weak interactions (hydrogen bonds, hydrophobic interactions, ionic bonds) and, in some cases, covalent disulfide bonds.
• Denaturation: Agents like heat or urea can disrupt the tertiary structure, leading to loss of function.

4. Quaternary Structure

• Definition: The arrangement and interactions among multiple subunits in proteins such as hemoglobin.
• Significance: The quaternary structure is essential for the protein’s function and stability.

Clinical Correlate: Gray Baby Syndrome

Gray baby syndrome is a serious condition that occurs in newborns, especially premature infants, exposed to chloramphenicol, an antibiotic used to treat bacterial infections, including meningitis. Due to the insufficient activity of UDP-glucuronyl transferase, these infants cannot excrete the drug effectively. This leads to severe complications, including:

• Symptoms:
  • Cyanosis (blue lips, nail beds, and skin)
  • Low blood pressure
  • Potentially fatal outcomes

Points to Remember

• Protein folding is critical for biological activity.
• There are four levels of protein structure: primary, secondary, tertiary, and quaternary.
• Secondary structures are stabilized by hydrogen bonds.
• Tertiary structures involve the overall 3D arrangement of the protein, stabilized by weak interactions and disulfide bonds.
• Quaternary structures describe interactions among multiple subunits in proteins.
• Gray baby syndrome highlights the importance of understanding protein folding and drug metabolism in clinical settings.

Bibliography

1. Lodish, H., Berk, A., Kaiser, C. A., & Scott, M. P. (2008). Molecular Cell Biology. 6th ed. W. H. Freeman.
2. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular Biology of the Cell. 4th ed. Garland Science.
3. Schmid, J., & Götz, S. (2015). “Chloramphenicol in the newborn: risks and benefits.” European Journal of Pediatrics, 174(9), 1197-1203. doi:10.1007/s00431-015-2585-5.