Proteins

Overview of Amino Acids and Protein Structure

• Learning Outcomes: Understanding protein structure and function is crucial for biological processes.

• Alzhimers’s: Amyloid B, Tau protein

• Parkinson’s:Amyloid B, Tau protein, a-synclein

• CJD: Tau protein, prions

• Transthyretin Amyloidosis: Transthyretin

Amino Acids

• General Structure: Amino acids have a central alpha carbon bonded to:

  • An amine group (NH2)

  • A carboxylic acid group (COOH)

  • A hydrogen atom

  • A variable R group (radical group) affecting properties.

• Classification:

  • Polar Amino Acids: Hydrophilic, capable of forming hydrogen bonds.

    • Asparagine, Glutamine, Tyrosine, Serine, Threonine.

  • Charged Amino Acids: Fully charged R groups, can be acidic or basic (e.g., lysine, glutamate).

    • Aspartic acid, Glutamic acid, Arginine, Lysine, Histidine.

  • Hydrophobic Amino Acids: Nonpolar and repels water.

    • Glycine, Alanine, Valine, Leucine, Isoleucine, Tryptophan, proline, cysteine, Methionine, phenylalanine.

Protein Structure

• Levels of Protein Structure:

  • Primary Structure: Sequence of amino acids in a polypeptide chain.

    • The amino group reacting with carboxylic acid from second R to make a peptide bond

      • its rigid but it can rotate

  • Secondary Structure: Regions stabilized by hydrogen bonds, forming:

    • Alpha Helices

      • Forms a right-handed coil, stabilized by partially negative oxygen and partial positive hydrogen bond

      • 3.6 aminos is included in each turn

      • Common in fibrous proteins like keratin

        • wool,hair, skin and nails.

    • Beta-Pleated Sheets

      • Stabilized by hydrogen bonds between adjacent polypeptide chains.

      • Found in proteins like silk.

  • Tertiary Structure: 3D shape formed through interactions between R groups, including:

    • Hydrogen bonds

    • Ionic bonds (salt bridges)

    • Van der Waals forces

    • Hydrophobic interactions.

  • Quaternary Structure: Assembly of multiple polypeptide chains into a functional protein (e.g., hemoglobin with 4 subunits).

Importance of Protein Folding

• Molecular Chaperones: Proteins that assist in the proper folding of other proteins after synthesis. Example: Heat Shock Proteins (HSPs).

  • HSP70 recognizes exposed, unfolded regions of new protein chains, especially hydrophobic regions. ( they bind until effective folding occurs)

  • 90 uses GroEL as well

• Folding Mechanism: Proteins achieve their functional conformation based on the amino acid sequence.

• Misfolding Consequences: Misfolded proteins can lead to diseases like Alzheimer’s, Parkinson’s, and amyloidosis, which may disrupt cell functions.

Enzymatic Functions

• Enzymes: Biological catalysts that speed up chemical reactions.

  • Typically proteins, though some RNA molecules (ribozymes) can also catalyze reactions.

• Specificity: Each enzyme has a specific substrate and catalyzes a specific reaction (e.g., lipases for lipids, proteases for proteins).

• Enzyme Functionality: Enzymes remain unchanged after reactions and can be reused. The substrate undergoes transformation to form products.

• Factors Affecting Enzyme Activity:

  • Temperature, pH, and salt concentration all influence protein shape and activity.

Diverse Roles of Proteins

• Functional Diversity: Proteins perform a wide range of functions in biological systems, including:

  • Structural roles (e.g., collagen in connective tissues)

  • Transport roles (e.g., hemoglobin in oxygen transport)

  • Regulatory functions (e.g., enzymes, signaling molecules).

• Proteins in Different Cell Types: Different cells express specific proteins, leading to varied cell morphologies and functions despite sharing the same DNA.

Conclusion

• Key Takeaway: The structure of proteins, dictated by their amino acid sequences and folding processes, is vital for their diverse functions in living organisms. Proper folding is crucial, as misfolding can lead to significant health issues.