Amino Acids

1°, 2°, 3°, and 4° structure of proteins

• 1° structure linkage is the peptide bond between amino acids
• 2° structure is the local folding of the polypeptide chain into alpha helices and beta sheets, stabilized by hydrogen bonds.
• 3° structure is the overall 3D shape of a protein, determined by interactions between R groups, including hydrophobic interactions, hydrogen bonds, ionic bonds, and disulfide bridges.
• 4° structure is the assembly of multiple polypeptide subunits into a functional protein complex, stabilized by the same interactions as 3° structure.

Practice Questions

Which of the following is NOT a component of the primary structure of a protein? Type the letter of the answer: Disulfide bonds

a. Peptide bonds - because they link amino acids
b. Side chains - because they are not included until tertiary structure
c. Amide bonds - because they are not found in protein structure
d. Hydrogen bonds - because they are part of secondary structure


Which of the following begins during the tertiary structure of a protein? Type the letter of the answer: Hydrophobic interactions

a. Hydrophobic interactions
b. Intermolecular forces
c. Ionic bonds
d. Peptide bonds

Amino Acid Properties

• Nonpolar amino acids have hydrophobic side chains that do not interact favorably with water.
• Polar amino acids have side chains that can form hydrogen bonds with water, making them hydrophilic.
• Charged amino acids have side chains that can gain or lose protons, resulting in positive or negative charges at physiological pH.

Dive deeper: The primary structure dictates all higher-order structures. Alpha helices have a right-handed twist and are stabilized by hydrogen bonds every 4 residues, while beta sheets can be parallel or antiparallel, with hydrogen bonds between strands. In a tertiary structure, hydrophobic interactions drive folding, where nonpolar residues cluster inside the protein, away from the aqueous environment. The quaternary structure involves multiple polypeptide chains, which can be identical or different, forming a functional protein complex.

Protein Structure and Function

• Protein folding is driven by the hydrophobic effect, where nonpolar side chains cluster away from water, and polar side chains interact with the aqueous environment
• Cysteine can form disulfide bonds, which are covalent linkages that stabilize protein structure.
• Proline introduces kinks in the polypeptide chain, affecting overall folding
• Conformational stability of proteins is influenced by factors such as pH and temperature.
• Denaturation is the loss of protein structure and function due to factors like heat, pH changes, or chemical agents
• Hydrophobic interactions play a crucial role in protein folding and stability, as nonpolar side chains tend to avoid contact with water, driving the folding process.

Dive deeper: Nonpolar residues cluster in the protein core due to the hydrophobic effect, making it the primary driving force of protein folding. Since cysteine can form disulfide bonds, a reducing agent can break these bonds. Since proline introduces kinks, it is often found at the beginning of alpha helices or in turns. While methionine is sulfur-containing, its chemical structure does not allow for the formation of disulfide bridges. Changes in pH disrupt non-covalent interactions like hydrogen bonds and ionic bonds, affecting secondary, tertiary, and quaternary structures. Primary structure, held by covalent peptide bonds, is generally unaffected by denaturation.

Practice Questions