Protein Structure — Summary (Professor Dave) 🧬

Key Concepts

• Proteins = polypeptides: polymers of amino acids (monomers).
• Functions: enzymes, receptors, hemoglobin (O2 transport), structural (muscle/organs), signaling, etc.

How amino acids polymerize

• Peptide bond formation: dehydration (condensation) reaction — loss of H₂O forms an amide (peptide) bond between amino acids.
• Terminology:
  • Dipeptide: 2 amino acids
  • Oligopeptide: 3–10 residues
  • Polypeptide / protein: >10 residues (typical proteins ~300–1000 aa)
• Chain orientation:
  • N-terminus (amino end) — conventionally left
  • C-terminus (carboxyl end) — conventionally right
  • Each monomer = residue

Levels of protein structure

1. Primary structure

   • Linear sequence of amino acids (one-letter or three-letter codes).
   • Sequence determines folding and function.

2. Secondary structure

   • Localized backbone conformations (few dozen residues).
   • Backbone is relatively planar due to partial double-bond (resonance) character of the peptide bond → limited rotation.
   • Driven by dipole/dipole (H-bond-like) interactions to lower energy.
   • Common motifs:
     • Alpha helix: spiral, ~3–4 residues/turn; R groups point outward; H-bonds between residue i and i±3/4.
     • Beta-pleated sheet: extended strands aligned side-by-side; NH—C=O interactions between strands.
   • Other coils/loops also occur.

3. Tertiary structure

   • Overall 3D fold of a single polypeptide.
   • Stabilized by:
     • Hydrophobic effect: nonpolar side chains buried inside
     • Hydrophilic residues: on surface interacting with solvent
     • Electrostatic interactions (dipole-dipole, ionic)
     • Disulfide bonds (cysteine—cysteine): covalent links that stabilize fold
   • Morphologies:
     • Globular proteins: compact, folded
     • Fibrous proteins: elongated, structural

4. Quaternary structure

   • Assembly of multiple polypeptide subunits (noncovalent interactions) into a functional complex (e.g., hemoglobin: 4 subunits).
   • Single-polypeptide proteins lack quaternary structure.

Important implications

• Sequence → structure → function: even a single amino acid change can drastically alter structure/function.
  • Example: Sickle cell disease — glutamic acid → valine in hemoglobin alters folding and causes sickled RBCs that block blood vessels.

Practical notes (for performing/understanding tasks)

• When analyzing protein sequences, use one-letter/three-letter codes to represent residues.
• Identify N- and C-termini for orientation.
• Predict secondary structure from local sequence (helix- or sheet-favoring residues).
• Consider hydrophobicity and possible cysteine pairs when reasoning about tertiary fold or stability.
• For multi-subunit proteins, examine interface interactions to understand quaternary assembly.

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