What is meant by tertiary structure of proteins?

Tertiary structure refers to the overall three-dimensional folding of a single polypeptide chain into a compact, globular shape

It arises after the secondary structure elements (α-helices and β-sheets) form and pack together through side-chain interactions

Stabilizing forces include

• Hydrophobic interactions where nonpolar side chains cluster away from water in the protein core

• Hydrogen bonds between polar side chains and between side chains and backbone atoms

• Ionic (electrostatic) interactions or salt bridges between oppositely charged side chains

• Disulfide bonds (covalent links) between cysteine residues, which lock regions of the chain into place

• Van der Waals forces contributing fine adjustments to side-chain packing

Tertiary structure creates functional sites

• Active sites of enzymes form pockets or clefts precisely shaped for substrate binding

• Ligand-binding sites and allosteric sites depend on the spatial arrangement of side chains

Domains are semi-independent folding units within tertiary structure

• Each domain often carries a distinct function (e.g., catalytic domain, binding domain)

• Domains can be recombined through evolution to create multifunctional proteins

Determination methods

• X-ray crystallography reveals atomic coordinates in crystalline proteins

• Nuclear magnetic resonance (NMR) spectroscopy maps distances between atoms in solution

• Cryo-electron microscopy visualizes large complexes and flexible regions

Misfolding or disruption of tertiary structure leads to loss of function and can cause diseases

• Examples include prion diseases and many amyloidoses where aberrant folding produces toxic aggregates

Correct tertiary folding is guided in vivo by molecular chaperones

• Chaperonins such as GroEL/GroES in bacteria provide isolated chambers for safe folding

• Heat-shock proteins bind unfolded chains to prevent aggregation and assist refolding