Interactions in Macromolecule Folding

Types of Interactions Maintaining Protein Shape

Covalent Bonds

Covalent bonds are very stable and require enzymes to break. Types of covalent bonds in proteins include:

Peptide Bonds

These bonds link amino acids together, forming the primary structure of the protein.

Disulfide Bridges

• Formed between two cysteine amino acids when their sulfhydryl (SH) groups are in close proximity.
• Involve a covalent bond between the sulfur atoms.
• Can be:
  • Intramolecular: Occurring between two cysteines within the same polypeptide chain (monomeric protein).
  • Intermolecular: Occurring between two cysteines on different polypeptide chains (multimeric protein), such as between alpha and beta globin chains in hemoglobin.

Non-Covalent Bonds

Weaker forces that are more easily disrupted. Examples include:

Hydrogen Bonding

• Occurs between R groups of amino acids.
• Donors: Typically -OH or amine groups.
• Acceptors: Typically carbonyl or sulfhydryl groups.

Ionic Bonds

• Occur between positively and negatively charged R groups.
• Can occur over large distances in the amino acid chain, as long as the R groups are close together after folding.
• Can be disrupted by changes in pH, leading to protein denaturation.

Van der Waals Interactions

• Transient interactions between electrons in orbitals.
• When electrons in one R group are positioned such that they create a temporary slight positive charge near a negative charge on another R group, this allows interaction.
• Different from ionic bonds because they are not constant; they disappear as electrons move.

Hydrophobic Interactions

• Hydrophobic amino acids tend to cluster toward the center of the protein to avoid exposure to water.
• This interaction helps to stabilize the protein structure by minimizing contact between hydrophobic R groups and the aqueous environment.

Protein Structure Levels

The shape and overall structure of a protein are described in four levels of organization:

• Primary
• Secondary