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

Proteins – Cambridge International AS & A Level Biology (9700)

Proteins are polymers of amino‑acid residues that fold into highly specific three‑dimensional shapes. The shape determines a protein’s function, and the stability of that shape is governed by a hierarchy of structural levels and a range of intra‑molecular interactions.

1. Amino‑Acids, Peptide Bonds and the Protein Backbone

General structure of an α‑amino‑acid

• Central (α) carbon attached to four groups: –NH₂ (amino), –COOH (carboxyl), a hydrogen atom, and a variable side chain (R).
• The side chain (R) gives each of the 20 standard amino‑acids its unique chemical properties.

Formation of a peptide bond (condensation reaction)

1. The carboxyl group of one amino‑acid reacts with the amino group of the next.
2. A molecule of water is released (‑OH from the carboxyl and ‑H from the amino).
3. The resulting covalent bond –C(=O)–NH– is planar and rigid, creating the protein backbone.

Suggested diagram: labelled α‑amino‑acid and a schematic of two residues linked by a planar peptide bond.

2. Levels of Protein Structure

3. Interactions that Hold Protein Molecules in Shape

Four main forces stabilise the three‑dimensional conformation of proteins. The first three are non‑covalent; the fourth is covalent.

3.1 Hydrophobic Interactions

• Non‑polar side chains (Leu, Ile, Val, Phe, Met, Trp, Ala) avoid water and cluster in the interior of the protein.
• Driven by an increase in the entropy of surrounding water molecules.
• Provides the principal driving force for the initial collapse of the polypeptide chain into a compact core.
• Each individual contact is weak, but the cumulative effect is large.

3.2 Hydrogen Bonding

• Occurs when a hydrogen attached to an electronegative atom (donor) interacts with another electronegative atom (acceptor).
• Backbone donors/acceptors: N‑H ↔ C=O (stabilises α‑helices and β‑sheets).
• Side‑chain donors/acceptors: –OH (Ser, Thr), –NH₂ (Asn, Gln), carbonyl groups, etc.
• Typical bond energy: 1–5 kcal mol⁻¹.
• Stabilises secondary structures and contributes to tertiary contacts.

3.3 Ionic (Salt‑Bridge) Bonding

• Electrostatic attraction between oppositely charged side chains, e.g. Lys⁺/Arg⁺ with Asp⁻/Glu⁻.
• Strength is enhanced in the low‑dielectric interior of the protein.
• Helps to position secondary‑structure elements relative to one another.
• Can be disrupted by changes in pH or ionic strength.

3.4 Covalent Bonding – Disulfide Bridges

• Two cysteine residues are oxidised to form a –S–S– linkage.
• Disulfide bridges are the only covalent interactions normally found in native proteins (syllabus wording).
• Much stronger than the non‑covalent forces listed above.
• Provides rigidity and resistance to denaturation, especially in extracellular proteins where the environment is oxidising.
• Reducing agents (e.g., β‑mercaptoethanol, dithiothreitol) break disulfide bonds, often leading to loss of tertiary structure.

4. Globular vs. Fibrous Proteins

5. Structure–Function Illustrations

5.1 Hemoglobin

• Quaternary structure: heterotetramer (α₂β₂).
• Each subunit contains a heme group – a planar porphyrin ring with an Fe²⁺ ion that binds O₂.
• Co‑operative binding: binding of O₂ to one subunit increases the affinity of the remaining subunits (allosteric effect).
• Stabilised by a mixture of hydrophobic contacts, H‑bonds, salt bridges and, in some species, disulfide links.

5.2 Collagen

• Primary structure: repeating Gly‑X‑Y tripeptide (X and Y are frequently Pro or hydroxy‑Pro).
• Three left‑handed helices intertwine to form a right‑handed triple helix (tertiary structure).
• Hydrogen bonds between the three chains give tensile strength; extensive disulphide cross‑linking between fibrils stabilises connective tissue.
• Key functional role: provides structural support in skin, bone, tendon and cartilage.

6. Summary of Interactions that Stabilise Protein Shape

7. Linkage to Other Syllabus Topics

8. Key Points for Revision

1. Proteins consist of amino‑acid residues linked by planar peptide bonds; the sequence (primary structure) dictates all higher‑order structures.
2. Four hierarchical levels of structure: primary → secondary → tertiary → quaternary.
3. Hydrophobic interactions drive the collapse of the polypeptide chain into a compact, water‑excluding core.
4. Hydrogen bonds stabilise regular secondary structures (α‑helix, β‑sheet) and contribute to tertiary contacts.
5. Salt bridges (ionic bonds) add specificity and are sensitive to pH and ionic strength.
6. Disulfide bridges are the only common covalent links in native proteins and confer extra stability, especially to extracellular proteins.
7. Globular proteins are soluble in water and usually functional (enzymes, transport, hormones, antibodies); fibrous proteins are insoluble and provide mechanical strength.
8. Hemoglobin’s quaternary structure enables cooperative O₂ binding; collagen’s Gly‑X‑Y repeat and triple‑helix give tensile strength to connective tissues.