BICH 410 Ch 6 Protein Structure 1.6.22

Chapter 6: Proteins - Three-Dimensional Structure

Overview of Protein Structure

• Classification of Proteins:

  • Globular Proteins: Soluble in water, functional diversity, often spherical.

  • Fibrous Proteins: Insulin, mechanical strength, structural roles, often insoluble.

• Four Levels of Protein Structure:

  1. Primary Structure (1°): Amino acid sequence; determined by covalent bonds of peptide bonds.

  2. Secondary Structure (2°): Local structures formed by hydrogen bonds; examples include alpha helices (α-helix) and beta sheets (β-sheet).

  3. Tertiary Structure (3°): Overall three-dimensional shape resulting from non-covalent interactions (hydrogen bonds, ionic interactions, hydrophobic interactions, van der Waals forces).

  4. Quaternary Structure (4°): Arrangement of multiple polypeptide chains (subunits) into a functional protein.

Primary Structure

• Details: The sequence of amino acids in a polypeptide chain determines the protein's primary structure.

  • Example Sequence: Lys - Ala - His - Gly - - - - Lys - Lys - Val - Leu - - Gly - Ala.

Secondary Structure

• Constraints and Stability:

  • The planar peptide bond limits flexibility in the polypeptide chain.

  • Key Structures:

    • α-Helix: Stabilized by hydrogen bonds between C=O of one residue and N-H of another 4 residues earlier.

    • β-Sheet: Composed of multiple β-strands, connected by hydrogen bonds. Can be parallel or antiparallel.

    • β-Turns: Allow the peptide chain to reverse direction; crucial between β-strands in sheets.

Tertiary Structure

• Formation and Stability:

  • Stabilized by interactions among hydrocarbon side chains, leading to a dense core of nonpolar residues and surface polar residues.

  • Techniques for Structure Determination: X-ray crystallography, NMR spectroscopy.

• **Core vs. Surface:

  • Core:** Typically made of α-helices and β-sheets.

  • Surface: Composed of loops and turns that interact with other molecules.

  • Importance of Motion: Enables functional interactions and biological activity within the protein.

Quaternary Structure

• Characteristics:

  • Composed of multiple subunits, exhibiting closed or open symmetry.

  • Interactions among subunits lead to cooperative and regulatory functions in proteins (example: hemoglobin).

Stability and Folding of Proteins

• Key Forces Stabilizing Protein Structure:

  • Primarily hydrophobic effects, supported by hydrogen bonding and electrostatic interactions.

  • Denaturation: Disruption due to heat or chemical agents, causing loss of structure and function.

  • Protein Folding: Folding pathways typically lead proteins from high energy and entropy configurations to lower states through guided conformational changes.

Intrinsically Disordered Proteins

• Many proteins exist in partially unfolded states, necessary for their biological roles (e.g., transcription factors).

Summary of Key Concepts

1. Weak Interactions Stabilize Structure: Non-covalent interactions are crucial for maintaining protein configurations.

2. Structural Definitions: Clear distinction between 1° to 4° structures affects protein function.

3. Protein Dynamics: Coiled coils, β-pleated sheets, α-helices—molecules capable of significant molecular motion support essential biological processes.

4. Quaternary Structure Advantages: Enhances stability, allows complex enzymatic activity, and supports evolutionary adaptability.