describe the types of interaction that hold protein molecules in shape: hydrophobic interactions, hydrogen bonding, ionic bonding, covalent bonding, including disulfide bonds

Published by Patrick Mutisya · 14 days ago

Proteins – Cambridge A‑Level Biology 9700

Proteins

Proteins are polymers of amino acids that fold into specific three‑dimensional shapes. The stability of these shapes is governed by a hierarchy of non‑covalent and covalent interactions. Understanding each type of interaction helps explain how proteins achieve their functional conformations.

Types of Interaction that Hold Protein Molecules in Shape

  • Hydrophobic interactions

  • Hydrogen bonding

  • Ionic (electrostatic) bonding

  • Covalent bonding – disulfide bridges

1. Hydrophobic Interactions

Non‑polar side chains (e.g., \$ \text{Leu}, \text{Ile}, \text{Val}, \text{Phe}, \text{Met} \$) tend to avoid water and cluster together in the interior of the protein. This aggregation is driven by the increase in entropy of surrounding water molecules.

  • Occurs mainly in the protein core.

  • Provides the main driving force for the initial collapse of the polypeptide chain.

  • Strength per interaction is modest, but many such contacts give a substantial cumulative effect.

2. Hydrogen Bonding

A hydrogen bond forms when a hydrogen atom covalently attached to an electronegative atom (donor) interacts with another electronegative atom (acceptor). In proteins, common donors and acceptors are the backbone carbonyl oxygen and amide hydrogen, as well as side‑chain groups such as \$ -OH \$ (Ser, Thr) and \$ -NH_2 \$ (Asn, Gln).

  • Stabilises secondary structures: α‑helices and β‑sheets.

  • Can also occur between side chains, contributing to tertiary structure.

  • Typical bond energy: 1–5 kcal mol⁻¹.

3. Ionic (Electrostatic) Bonding

Ionic bonds arise from attractions between oppositely charged side chains, such as \$ \text{Lys}^{+} \$/\$ \text{Arg}^{+} \$ and \$ \text{Asp}^{-} \$/\$ \text{Glu}^{-} \$. These interactions are sometimes called salt bridges.

  • Strength depends on the dielectric constant of the surrounding medium; stronger in the low‑dielectric protein interior.

  • Help to position secondary‑structure elements relative to each other.

  • Can be disrupted by changes in pH or ionic strength.

4. Covalent Bonding – Disulfide Bridges

When two cysteine residues are oxidised, their thiol groups form a covalent disulfide bond (\$\text{–S–S–}\$). This bond is much stronger than the non‑covalent interactions listed above.

  • Provides rigidity and resistance to denaturation.

  • Common in extracellular proteins where the oxidising environment favours disulfide formation.

  • Can be reduced by agents such as β‑mercaptoethanol, leading to loss of tertiary structure.

Summary Table

InteractionNature of BondTypical Residues InvolvedRole in Protein Structure
Hydrophobic interactionsEntropic effect; non‑polar side chains clusterLeu, Ile, Val, Phe, Met, Trp, AlaCore formation; drives initial folding
Hydrogen bondsPartial electrostatic attraction (H‑donor ↔ H‑acceptor)Backbone C=O and N‑H; side‑chains –OH, –NH₂, carbonylsStabilises α‑helices, β‑sheets, tertiary contacts
Ionic (salt bridges)Electrostatic attraction between opposite chargesLys⁺, Arg⁺, His⁺, Asp⁻, Glu⁻Positions secondary‑structure elements; pH‑sensitive
Disulfide bondsCovalent S–S linkageCysteine (Cys)Provides rigidity; stabilises extracellular proteins

Suggested diagram: schematic of a folded protein showing hydrophobic core, α‑helix with hydrogen bonds, a salt bridge, and a disulfide bridge.

Key Points for Revision

  1. Proteins are stabilised by a combination of weak (non‑covalent) and strong (covalent) interactions.

  2. Hydrophobic interactions are the primary driving force for the collapse of the polypeptide chain.

  3. Hydrogen bonds are essential for secondary‑structure formation.

  4. Ionic bonds (salt bridges) add specificity and can be modulated by pH.

  5. Disulfide bridges are the only covalent links that commonly occur in native proteins and are crucial for extracellular stability.