Secondary Structure of Proteins

Secondary Structure Basics - The Local Folds

• Local, regular, repeating 3D arrangements of the polypeptide backbone.
• Stabilized mainly by hydrogen bonds between backbone C=O and N-H groups.
• Peptide Bond:
  • Planar & rigid (partial double bond character).
  • No rotation around C-N bond.
• Key Dihedral Angles:
  • Phi ($\phi$): Rotation around N-C$\alpha$ bond.
  • Psi ($\psi$): Rotation around C$\alpha$-C bond.
• Ramachandran Plot:
  • Maps sterically allowed ($\phi$, $\psi$) combinations.
  • Predicts stable conformations.

⭐ Hydrogen bonds between backbone amide (N-H) and carbonyl (C=O) groups are crucial for stabilizing secondary structures.

Alpha-Helix - Coiling Up Right

• Right-handed coiled polypeptide chain; most common regular secondary structure.
• Stabilized by intrachain H-bonds:
  • Between carbonyl O (residue $n$) & amide H (residue $n+4$).
• Key Parameters:
  • 3.6 residues per turn.
  • Pitch (axial distance/turn): 5.4 Å.
  • Rise per residue: 1.5 Å.
• Amino Acids:
  • Formers: Met, Ala, Leu, Glu, Lys (📌 Mnemonic: MALEK).
  • Breakers: Proline (causes kink, no N-H for H-bond), Glycine (too flexible).

⭐ Proline frequently disrupts alpha-helices because its ring structure creates a kink and it cannot form the necessary hydrogen bond.

Beta-Pleated Sheet - Folding Flat Out

• Composed of extended polypeptide segments called β-strands.
• Strands align laterally, forming a sheet; stabilized by inter-strand H-bonds (C=O···H-N).
• R-groups project alternately above and below the pleated sheet plane.
• Often rich in Glycine (Gly) & Alanine (Ala) due to small R-groups.

⭐ Silk fibroin is predominantly composed of anti-parallel β-pleated sheets, contributing to its strength and flexibility.

Turns & Loops - Connecting The Dots

• Connect α-helices & β-sheets; change chain direction abruptly.
• β-Turns (Reverse Turns):
  • Connect anti-parallel β-strands.
  • 4 amino acid residues. H-bond: CO (residue $i$) & NH (residue $i+3$).
  • Pro (pos 2) & Gly (pos 3) common. 📌 Pro-Gly "Turn Pair".
    • Pro: fixed φ angle for turn.
    • Gly: small, flexible.
  • Types I & II common.
• γ-Turns:
  • 3 amino acid residues. H-bond: CO (residue $i$) & NH (residue $i+2$).
• Loops:
  • Larger, less regular connecting segments.
  • Surface loops: interactions, recognition, active sites.

  • ⭐ Pro & Gly: "helix breakers", but crucial "turn makers". oka

Motifs & Fibers - Building Blocks & Backbones

• Supersecondary Structures (Motifs): α-helix & β-sheet combinations.
  • βαβ unit: α-helix links two parallel β-strands.
  • β-hairpin: Antiparallel β-strands connected by a turn.
  • Greek key: Four antiparallel β-strands forming a pattern.
• Fibrous Proteins: Elongated, structural roles; repetitive sequences.
  • α-Keratin: Coiled-coil of two α-helices (hair, nails); Cys-rich (disulfide bonds).
  • Silk Fibroin: Stacked antiparallel β-sheets (silk); Ala/Gly-rich; flexible.
  • Collagen: Unique triple helix (Gly-X-Y repeats; X=Pro, Y=Hyp). 📌 Glycine every 3rd residue.

    ⭐ Collagen: most abundant animal protein. Vitamin C needed for Pro/Lys hydroxylation, vital for stability.

High‑Yield Points - ⚡ Biggest Takeaways

• α-helix & β-pleated sheet are key secondary structures.
• Stabilized mainly by hydrogen bonds within the peptide backbone.
• α-helix: Right-handed coil, 3.6 residues/turn; features intrachain H-bonds.
• Proline (helix kink) & Glycine (too flexible) act as helix breakers.
• β-sheet: Comprises β-strands (parallel/antiparallel); H-bonds are often interchain.
• β-turns (reverse turns) connect antiparallel β-sheet strands, frequently containing Proline & Glycine.
• Ramachandran plot visualizes allowed φ and ψ backbone dihedral angles.