🧬 Structural Features of Proteins – Complete Guided Summary

🧩 2.1.1 From Primary to Quaternary Structure

Proteins are organized hierarchically, meaning structure builds step-by-step:

1️⃣ Primary structure

• The amino acid sequence
• Amino acids are linked by peptide bonds
• The repeating backbone unit is:
  • –N–Cα–C–
• This backbone (not side chains!) defines most structural rules

➡️ Key idea: Sequence encodes everything that follows.

2️⃣ Secondary structure

• Local, repetitive backbone conformations
• Typically 5–20 residues
• Stabilized by hydrogen bonds between backbone CO and NH
• Main types:
  • α-helices
  • β-strands / β-sheets
  • Turns

➡️ Important: Secondary structure depends on backbone geometry, not side-chain chemistry.

3️⃣ Tertiary structure

• The full 3D fold of a single polypeptide
• Distant residues in sequence can be neighbors in space
• Driven mainly by:
  • Hydrophobic core formation
  • Van der Waals interactions
  • Hydrogen bonds
  • Salt bridges

4️⃣ Quaternary structure

• Assembly of multiple folded chains
• Examples:
  • Homodimers (same subunits)
  • Heterotetramers (different subunits, e.g. hemoglobin)

➡️ Structure levels build like LEGO blocks 🧱

📐 2.1.2 Geometrical and Conformational Properties

🔄 Backbone dihedral angles (φ, ψ, ω)

Each amino acid backbone is defined by three torsion angles:

• Peptide bond has partial double-bond character
• Makes the peptide group planar
• Cis peptide bonds are rare (mostly X–Pro)

📊 Ramachandran plot

• Maps allowed φ/ψ combinations
• Steric clashes exclude large regions
• Glycine is special:
  • No side chain → much more flexible
• Secondary structures cluster in distinct regions:
  • α-helices (bottom left)
  • β-sheets (upper left)

➡️ If you see φ/ψ → think Ramachandran constraints.

🧷 Side-chain dihedral angles (χ angles)

• Side chains rotate around C–C bonds
• Named χ1, χ2, χ3…
• Preferred conformations:
  • ~60°, 180°, 300° (staggered)

Examples:

• Valine prefers χ1 ≈ 180°
• Leucine & Isoleucine prefer χ1 ≈ 300°
• Aromatic residues often have χ2 ≈ 90° (ring ⟂ backbone)

➡️ Side-chain geometry is constrained by backbone sterics.

🌀 2.1.3 Secondary Structure Elements

🧬 α-Helices

Most common helix type

Key features:

• Right-handed
• 3.6 residues per turn
• Rise: 1.5 Å per residue
• Hydrogen bonds: CO(n) → NH(n+4)

🧲 Helix macrodipole

• All peptide dipoles align
• Net charge:
  • + at N-terminus
  • – at C-terminus
• Influences helix–helix interactions

🧢 Helix capping

• Terminal residues lack H-bonds
• Specific residues stabilize ends:
  • N-cap: Gly, Ser, Asp, Asn
  • Special “capping box” motif: Ser–X–X–Glu

🌊 Amphipathic helices

• One hydrophobic face, one hydrophilic face
• Common in:
  • Globular proteins
  • Membrane pores
• Visualized using helical wheel diagrams

🧵 Other helices

• 3₁₀-helix
  • n → n+3 hydrogen bonds
  • Tighter, less stable
• π-helix
  • n → n+5 hydrogen bonds
  • Wider, rare
• Usually found at α-helix ends

🧻 β-Strands and β-Sheets

• Extended backbone conformation
• Side chains alternate above/below the sheet
• β-sheets formed by hydrogen bonding between strands

Types:

• Antiparallel β-sheets
  • Stronger, linear H-bonds
• Parallel β-sheets
  • Slightly weaker, angled H-bonds

🪢 β-bulges

• Extra residue causes local distortion
• Alters side-chain direction
• Common in antiparallel sheets

🔁 Turns and loops

β-Turns

• 180° chain reversal
• 4 residues
• CO(i) → NH(i+3) H-bond
• Types I, II, III (+ mirror types)

Residue preferences:

• Gly (flexibility)
• Pro (rigidity, especially at i+1)

➡️ β-turn between antiparallel strands = β-hairpin

Loops

• Irregular regions
• Surface-exposed
• Rich in polar/charged residues
• Energetically allowed φ/ψ values

🧠 2.1.7 Tertiary Structure

🏗️ What defines tertiary structure?

• Exact 3D position of every atom
• Stabilized by:
  • Hydrophobic core
  • Hydrogen bonds
  • Salt bridges
  • van der Waals contacts

💧 Hydrophobic effect (central driver)

• Hydrophobic residues cluster inside
• Hydrophilic residues remain outside
• Quantified by hydrophobicity scores
• Hydropathy index averages scores over ~19 residues

🧩 Backbone polarity problem:

• Backbone is polar → unfavorable inside core
• Solution:
  • α-helices & β-sheets maximize internal H-bonding

⚡ Buried polar residues

• If buried:
  • Must form H-bonds or salt bridges
• Often functionally important
  • Catalysis
  • Metal binding (e.g. SOD1)

🤝 Protein–protein interfaces

• Not purely hydrophilic
• Often include:
  • Hydrophobic patches
  • Aromatic residues
• Example:
  • Mia40 has a conserved hydrophobic cleft for substrate binding

🧬 2.1.8 Quaternary Structure

🧱 What is it?

• Assembly of multiple folded subunits
• Examples:
  • Dimers, trimers, tetramers

🔗 Stabilization

• Mainly hydrophobic interactions
• Also:
  • Hydrogen bonds
  • Electrostatic interactions
• Requires surface complementarity

🌀 Special case:

• Some subunits are partially unfolded alone
• Final structure forms only upon oligomerization
• Classic example: coiled-coil proteins

🧠 Big-Picture Takeaways (Exam Gold ⭐)

• Structure is hierarchical and constrained
• Backbone geometry (φ/ψ/ω) governs everything
• Secondary structures solve backbone polarity
• Hydrophobic core drives folding
• Quaternary structure relies on specific surface interactions