LECTURE BEFORE EXAM 1 - Comprehensive Notes on Protein Structure and Denaturation

Protein Structure and Function

Three-Dimensionality and Function

  • Amino acids are three-dimensional units.

  • Proteins, formed from these three-dimensional amino acids, are also inherently three-dimensional.

  • This three-dimensionality defines the protein's structure and shape.

  • The shape, in turn, dictates the protein's function.

  • If the shape or structure is altered or destroyed, the protein's function will be compromised.

The Native Fold

  • The formal, functional structure of a protein is termed the native fold.

  • This is the specific, energetically favorable conformation a protein adopts to perform its function.

  • Protein folding is driven by energetic considerations, aiming for stability.

  • Stability and reactivity are inversely related across the spectrum of molecular interactions.

Noncovalent Interactions in Protein Folding

  • Stable protein structures arise from numerous noncovalent interactions.

  • There are approximately seven broad types of noncovalent interactions:

    • Ion-ion interactions

    • Ion-dipole interactions

    • General dipole-dipole interactions

    • Hydrogen bonds

    • Van der Waals forces

    • Aromatic \pi (pi) stacking

    • Chelation

  • These weak interactions occur throughout a large protein, conferring its specific shape.

Hair Straightening Example

  • The curling of hair is due to disulfide linkages between cysteine residues in hair protein strands, giving the protein a particular shape.

  • Applying heat (e.g., with a hair straightener) breaks these disulfide bonds, causing the curl to be lost and the hair to become straight.

  • Similarly, proteins attain their specific stable shape based on inter-amino acid interactions.

Genetic Aberrations and Protein Folding

  • Under normal conditions, a protein will fold in the exact same way every time it is synthesized.

  • If a protein is synthesized abnormally (e.g., due to a genetic aberration), it will be malformed and unable to function optimally, leading to cellular dysfunction.

  • The native fold is created by numerous favorable noncovalent interactions (not covalent bonds) within the protein.

  • (Entropy Cost): The instructor briefly mentioned entropy cost is related to stability but decided to skip it in detail.

Favorable Interactions for Protein Stability

  • The following are key favorable interactions:

    • Hydrophobic Effect:

      • This involves the expulsion of water molecules from the solvation layer surrounding a protein as it folds.

      • It can be thought of as the protein