Macromolecules - Proteins Overview

Macromolecules - Proteins

• Proteins perform many functions in cells, including:
  • Catalyzing reactions (enzymes)
  • Providing support and shape (structural proteins)
  • Facilitating movement (motility proteins)
  • Controlling and coordinating cell function (regulatory proteins)
  • Transporting substances (transport proteins)
  • Communicating between cells (signaling proteins)
  • Responding to chemical stimuli from the environment (receptor proteins)
  • Protecting against disease (defensive proteins)
  • Serving as reservoirs of amino acids (storage proteins)

Monomers of Proteins

• The monomers of proteins are amino acids.
• Only 20 kinds of amino acids are used in protein synthesis.
• Every amino acid has the same basic structure.
• All amino acids in human body are L-amino acids.

Protein Structure Levels

• Primary Structure: The linear sequence of amino acids in a polypeptide chain.
• Secondary Structure: The local folding of the polypeptide chain, often into a-helices or β-sheets, stabilized by hydrogen bonds.
• Tertiary Structure: The overall three-dimensional shape of the polypeptide chain, stabilized by various interactions involving R-groups, including: hydrogen bonds, disulfide bonds, ionic bonds, Van der Waals forces, and hydrophobic interactions.
• Quaternary Structure: The arrangement of multiple polypeptide chains in a protein, stabilized by the same forces involved in tertiary structure.

Protein Sizes

• Proteins vary greatly in size.
• The largest protein is titin (34,350 amino acids).
• The smallest protein is insulin (51 amino acids).
• The average protein size is around 300 amino acids.
• Estimates exist of the number of different proteins of 100 amino acids that can be made with 20 amino acids.
• Data from various organisms are provided via plots to show protein size distributions.

Protein Folding

• The polypeptide chain folds into a specific 3-D shape due to the interactions of amino acid side chains (R groups).
• Covalent (peptide bonds and disulfide bonds) and non-covalent (hydrogen bonds, ionic bonds, Van der Waals forces, hydrophobic interactions) bonds are involved.
• The interactions between the amino acid side chains contribute to the specific 3-dimensional structure (folding) of the protein.

Protein Domains

• Proteins with similar functions often share common domains.
• Proteins with multiple functions may have separate domains for each function.

Protein Structure Prediction

• Primary structure determines the final folded shape of a protein.
• Tools like AlphaFold and AlphaFold2 create accurate 3D protein structure predictions.
• A database of predicted structures is available for research.

Quaternary Structure

• Quaternary structure describes how multiple polypeptide chains associate to form a multimeric protein.
• The type of interactions that hold the chains together are the same as those involved in maintaining tertiary structure.

Disease Prion Protein

• The disease prion protein PrPsc is characterized by its multimeric amyloid fibril, parallel in-register architecture, and high β sheet content.
• A comparative comparison with its healthy form PrPc is presented in terms of structure, including the primary and secondary forms.

Enzyme Characteristics and Regulation

• All enzymes have a specific active site with a particular shape for interactions with substrates.
• The active site interacts in specific ways with substrates, changing the substrate shape or causing temporary covalent bonds, leading to bond distortion, proton transfer, and electron transfer.
• Some enzymes require cofactors, like prosthetic groups (metal ions) or coenzymes (vitamin derivatives), to function.
• Enzymes are very specific to the substrate that they interact with.
• Enzyme function is highly sensitive to temperature changes, optimal activity occurring at a specific temperature.
• Enzyme function is also highly pH dependent, with activity varying greatly depending on pH.
• Enzyme activity can be regulated in numerous ways, including covalent modification, feedback inhibition, allosteric regulation, product inhibition, and proteolytic activation by reversible and irreversible inhibitors.
• Enzymes can be regulated by the addition or removal of chemical groups such as phosphorylation, dephosphorylation, methylation, demethylation, acetylation and deacetylation.