Denaturation = loss of the native 3D structure of a protein (secondary, tertiary, quaternary disrupted) while the primary structure (peptide bonds, amino acid sequence) remains INTACT.

Causes: Heat (breaks H-bonds, hydrophobic interactions), pH extremes (disrupts ionic bonds), organic solvents (disrupt hydrophobic core), heavy metal ions (Hg2+, Pb2+ — form bonds with -SH, -COO- groups), urea/guanidine HCl (disrupts H-bonds extensively), mechanical agitation (e.g., whipping egg whites).

Results: Loss of biological activity (enzyme becomes inactive), decreased solubility, increased digestibility (denatured proteins are more accessible to digestive enzymes — cooking makes protein foods more nutritious).

Examples: Coagulation of egg white on boiling, curdling of milk (casein denatured by acid from lactobacillus), precipitation of proteins by alcohol (hand sanitizers denature bacterial proteins).

Renaturation: Some small proteins can refold to native structure upon removal of denaturant (Anfinsen's experiment with ribonuclease A — proved that amino acid sequence determines 3D structure).