Tertiary and Quaternary Protein Structure
High-Yield Summary
- Tertiary structure = full 3D shape of one polypeptide chain, driven by R-group (side-chain) interactions: hydrophobic collapse, hydrogen bonds, salt bridges, disulfide bonds.
- Hydrophobic side chains bury in the interior away from water; this increases water's entropy and decreases Gibbs Free Energy — the thermodynamic driver of folding.
- Salt bridges = ionic interactions between oppositely charged side chains (e.g., Lys⁺/Glu⁻). Disulfide bonds = covalent bonds between two cysteine thiols.
- Quaternary structure = arrangement of multiple polypeptide chains into one functional protein; benefits include stability, less DNA needed, more efficient catalysis, and cooperativity (e.g., hemoglobin — O₂ binding at one subunit raises affinity at the others).
- Conjugated proteins need a prosthetic group: lipoprotein (lipid), glycoprotein (carbohydrate), nucleoprotein (nucleic acid).
- Denaturation disrupts tertiary/quaternary structure (unfolds the protein, breaks non-covalent + disulfide interactions) but usually leaves primary structure (sequence) intact. Caused by heat or solutes (urea, detergents); can be reversible or irreversible.
Key Terms
- Tertiary structure
- A single polypeptide chain's overall 3D fold, stabilized by side-chain interactions.
- Quaternary structure
- The specific arrangement of multiple polypeptide subunits into one functional protein complex.
- Salt bridge
- Ionic bond between oppositely charged side chains (e.g., Lys⁺ and Glu⁻).
- Cooperativity
- Binding at one subunit changes the binding behavior of other subunits — classic example: hemoglobin and O₂.
- Prosthetic group
- A non-protein molecule covalently attached to a conjugated protein and essential to its function.
- Denaturation
- Loss of tertiary/quaternary structure (unfolding) from heat or chemical solutes; primary structure typically survives.
Tertiary-Structure Stabilizing Interactions
| Interaction | Description |
|---|---|
| Hydrophobic interactions | Nonpolar side chains bury in the interior, away from water |
| Hydrogen bonds | Form between polar side chains |
| Salt bridges | Ionic bonds between oppositely charged side chains |
| Disulfide bonds | Covalent bonds between two cysteine thiol groups |
Conjugated Protein Types
- Lipoprotein
- Prosthetic group = lipid.
- Glycoprotein
- Prosthetic group = carbohydrate.
- Nucleoprotein
- Prosthetic group = nucleic acid.
Common MCAT Trap
- Denaturation breaks folding (tertiary/quaternary), NOT the peptide bonds of primary structure — sequence stays intact even when a protein is fully denatured.
- Hydrophobic burial is favorable because it increases the SOLVENT's (water's) entropy, not the protein's own entropy — a frequently inverted point.
- Quaternary structure only exists for multi-chain proteins; a single-chain protein tops out at tertiary structure.
Quick Recall
What thermodynamic quantity decreases when hydrophobic side chains bury in a protein's interior, and why does that favor folding?
What covalent bond links two cysteine residues, and what level of structure does it reinforce?
Give an example of cooperativity in quaternary structure.
Does denaturation typically affect primary structure?