How protein structure leads to function

Lecture 3

Protein function depends on 3D structure

The specific shape of a protein determines what it can bind and how it behaves. Even small structural changes can dramatically alter function.

Primary structure determines function

The amino acid sequence dictates how the protein folds, which in turn determines its biochemical role.

Hydrophobic core

Non‑polar residues cluster inside globular proteins, stabilizing the fold. This core is essential for maintaining shape and therefore function.

Protein surface chemistry

Hydrophilic and charged residues on the surface determine how proteins interact with water, membranes, other proteins, and ligands.

Binding sites

Formed by specific arrangements of amino acids; shape and chemistry allow selective binding of substrates, ligands, or other proteins.

Enzyme active sites

Specialized pockets where catalysis occurs; shaped precisely to stabilize transition states and promote chemical reactions.

Structural proteins

Proteins like collagen have repetitive, rigid structures that give mechanical strength. In animals, collagen is essential for connective tissues such as tendons, ligaments, and skin.

Collagen triple helix

Three tightly wound helices stabilized by glycine (for tight packing) and proline (for sharp bends). This structure gives tensile strength to animal tissues.

Globular proteins

Compact, folded proteins with hydrophobic cores and hydrophilic surfaces. Their shape allows dynamic functions such as catalysis, transport, and regulation.

Myoglobin structure–function relationship

Myoglobin’s compact globular fold creates a hydrophobic pocket for oxygen binding. In animals, especially diving mammals, high myoglobin concentration allows extended oxygen storage.

β‑barrel proteins

Formed by β‑strands arranged in a cylindrical shape. Example: retinal‑binding protein, where the barrel encloses a hydrophobic ligand.

α/β‑barrel proteins

Alternating α‑helices and β‑strands form a barrel with a central active site. Example: triose phosphate isomerase, a key glycolytic enzyme in animals.

Motifs contribute to function

Super‑secondary structures (βαβ units, α‑helical hairpins, Greek key motifs) create stable frameworks that support binding sites or catalytic regions.

Domains as functional units

Independently folding regions of a protein often correspond to specific functions (e.g., binding, catalysis, regulation).

Multidomain proteins

Many proteins contain multiple domains that work together or independently. Example: glyceraldehyde‑3‑phosphate dehydrogenase has two domains that cooperate in catalysis.

Quaternary structure and function

Arrangement of multiple subunits affects activity. Example: HIV protease is a dimer; both subunits are required for its catalytic function.

Antibody structure–function relationship

Immunoglobulins use modular domains to create flexible, specific antigen‑binding sites. Their quaternary structure allows two identical binding arms.

Immunoglobulin domain

A stable β‑sheet sandwich stabilized by a disulphide bond; widely used in extracellular animal proteins for recognition and adhesion.

Epitope recognition

Antibodies bind specific surface features (epitopes) on antigens, enabling precise immune targeting.

Protein misfolding consequences

Incorrect folding disrupts function and can lead to disease. In animals, misfolded proteins can cause aggregation disorders (e.g., misfolded collagen leading to connective tissue defects).