CHE414 Lecture 6 (Primary, Secondary, and Tertiary Structure; F24)

*lecture 5 has titration curve practice

Proteins

• Definition: Chains of amino acids linked by peptide bonds.

• Folding: Polypeptide chains fold into various shapes (loops, helices, sheets).

• Function Types: Enzymes, carriers, regulations, and structural components.

Levels of Protein Structure

Primary Structure

• Definition: The specific sequence of amino acids in a polypeptide chain.

  • Example: Asp-Ala-Gly-Ser-Trp

Secondary Structure

• Definition: The spatial arrangement of polypeptide backbone, stabilized by hydrogen bonding.

  • Types:

    • Alpha helices: Coils formed by hydrogen bonding in the backbone.

    • Beta sheets: Extended chains forming sheets through hydrogen bonding.

Tertiary Structure

• Definition: The three-dimensional structure of a polypeptide, including interactions among R groups.

Quaternary Structure

• Definition: Interaction between multiple subunits; not all proteins exhibit this feature.

Peptide Bond Formation

• Process: Formation occurs via a condensation reaction.

  • N-terminus: Free amino group at the beginning.

  • C-terminus: Free carboxylate group at the end.

Drawing Peptides

• Practice: Create dipeptides, tripeptides, etc.

• Example: C-A-T as a demonstration.

Peptide Bond Structure

• Planarity: Carbonyl O and C, amide N and H, and alpha carbons are coplanar.

• Conformations: Two main forms exist – cis and trans.

  • Steric Hindrance: Cis configuration has steric strain; trans is favored except with proline, which can exist in both conformations.

Bond Rotation

• Phi (φ) and Psi (ψ): Angles of rotation around N-Cα and Cα-C bonds respectively.

Ramachandran Plots

• Purpose: Visualize permitted phi and psi angles for amino acids.

• Areas:

  • Blank: Non-permissible values.

  • Colored: Ideal secondary structures.

Secondary Structure Features

• Hydrogen Bonding: Backbone hydrogen bonds critical; R groups do not influence secondary structure.

Alpha Helix

• Characterization: First modeled by Linus Pauling, Robert Corey, Max Perutz.

• Hydrogen Bonding Pattern: Between carbonyl O of residue n and amine H of residue n+4.

  • ex. Carbonyl O of c1 will hydrogen bond to…

    • 1+4=5 → amine H of residue 5, forming a characteristic helical structure (R—NH)

• Physical Measurements:

  • Pitch: 0.54 nm (advance per turn)

  • Rise: 0.15 nm (advance per amino acid).

Beta Strands and Sheets

• Structure: Beta strands form extended structures that can align to form sheets stabilized by hydrogen bonds.

  • Configurations: Parallel (same direction) or antiparallel (opposite direction).

Connecting Secondary Structures

• Turns and Loops: Allow direction changes; loops term for all types, with short loops called turns.

• Common Residues: Some amino acids are prevalent in these structures.

  • ex. proline and glycine because they disrupt the regularity of helical backbone conformation

Tertiary Structure

• Definition: Result of polypeptide folding into a stable 3D shape influenced by R groups.

Tertiary Stabilization

• Hydrophobic Core: Globular proteins have hydrophilic surfaces and hydrophobic interiors.

  • Hydrophobicity: The greater a residue's hydrophobicity, the more likely it is to be in the interior.

Protein Domains

• Characteristics: Proteins may contain multiple domains, which can be responsible for different functions.

Tertiary Structure Determinants

• Major Determinants: Ionic pairs, disulfide bonds, and zinc fingers contribute to protein stability and folding.

• Types of Interactions:

  • Ion Pairs: Between oppositely charged groups

  • Disulfide Bonds: Between Cys residues

  • Zinc Fingers: Help some small proteins fold.