Protein structure

Primary structure is the linear sequence of amino acids joined by peptide bonds, written from the N-terminus to the C-terminus and encoded directly by the gene. Secondary structure describes local folding — alpha helices and beta pleated sheets — stabilized by hydrogen bonds between backbone amide and carbonyl groups, not between side chains. Proline disrupts helices because its ring locks the backbone, and glycine's flexibility makes it common in turns.

Tertiary structure is the full three-dimensional shape of a single polypeptide, driven largely by the hydrophobic effect: nonpolar side chains bury themselves away from water while polar and charged residues face outward. Hydrogen bonds, ionic salt bridges, van der Waals contacts, and covalent disulfide bonds between cysteine residues stabilize the fold. Quaternary structure exists only in proteins built from more than one polypeptide chain — hemoglobin's four subunits are the standard example — and enables cooperative behavior such as hemoglobin's sigmoidal oxygen binding curve.

Because function follows shape, disrupting the higher levels destroys activity. Denaturation by heat, extreme pH, urea, or detergents unfolds a protein while leaving peptide bonds intact, so primary structure survives. A single amino acid substitution in the primary sequence can propagate upward, as in sickle cell disease, where a glutamate-to-valine change in the beta globin chain creates a hydrophobic patch that drives polymerization of deoxygenated hemoglobin. Chaperone proteins assist correct folding, and misfolding underlies amyloid and prion diseases.

The MCAT tests protein structure in both the biology/biochemistry and chemistry/physics sections. Be ready to identify which bonds stabilize each level, predict how a mutation or a change in pH or temperature affects folding, and connect quaternary structure to cooperativity and allosteric regulation.