41. Which one of the following is the most appropriate statement regarding folded proteins?
(1) Charged amino acid side chains are always buried.
(2) Charged amino acid side chains are seldom buried.
(3) Non-polar amino acid side chains are seldom buried.
(4) Tyrosine residues are always buried.

Protein Folding and Amino Acid Side Chain Distribution

Understanding the spatial arrangement of amino acid side chains in folded proteins is crucial for deciphering protein structure and function. Different amino acids have distinct preferences based on hydrophobicity, charge, and polarity.

Correct Answer:

The correct option is (2) Charged amino acid side chains are seldom buried.

Explanation:

(1) Charged Amino Acid Side Chains Are Always Buried ❌ (Incorrect)

• Charged residues (e.g., Asp, Glu, Lys, Arg, His) are hydrophilic and tend to be exposed on the protein surface.
• Some exceptions exist in enzyme active sites, but burial is not the rule.

(2) Charged Amino Acid Side Chains Are Seldom Buried ✅ (Correct)

• Most charged residues are found on the surface of folded proteins, where they interact with the aqueous environment.
• Exceptions: When buried, they often participate in salt bridges or hydrogen bonding to maintain stability.

(3) Non-Polar Amino Acid Side Chains Are Seldom Buried ❌ (Incorrect)

• Non-polar (hydrophobic) amino acids (e.g., Val, Leu, Ile, Phe) prefer to be buried inside the protein core.
• This reduces water interaction, stabilizing the folded structure.

(4) Tyrosine Residues Are Always Buried ❌ (Incorrect)

• Tyrosine (Tyr) has a hydrophobic benzyl ring but also a hydroxyl (-OH) group, making it amphipathic.
• It can be found both buried and exposed, depending on the protein.

Thus, the correct answer is (2) Charged amino acid side chains are seldom buried.

Nearby Topics for Better Understanding

1. Hydrophobic vs. Hydrophilic Amino Acids

• Hydrophobic amino acids: Found in the core of proteins.
• Hydrophilic amino acids: Found on the surface interacting with water.

2. Salt Bridges and Hydrogen Bonding in Protein Folding

• Salt bridges (electrostatic interactions) help stabilize proteins when charged residues are buried.
• Example: Lysine and Glutamate forming a salt bridge in enzyme active sites.

3. Role of Tyrosine in Protein Stability

• Amphipathic nature allows tyrosine to be found in both the core and surface.
• Example: Tyrosine residues in transmembrane proteins help anchor them in membranes.

4. Protein Misfolding and Disease

• Misfolded proteins with incorrect hydrophobic/hydrophilic distribution can lead to diseases like Alzheimer’s and cystic fibrosis.

Conclusion

Folded proteins typically bury hydrophobic residues in the core while exposing hydrophilic and charged residues on the surface. Charged amino acids are seldom buried unless stabilized by interactions such as salt bridges. This principle is key to understanding protein stability and function.