1.7 Proteins

A peptide bond forms through a dehydration synthesis reaction in which the carboxyl group (−COOH) of one amino acid reacts with the amine group (−NH₂) of the next amino acid. This covalent bond links the two amino acids, releasing one molecule of water and extending the growing polypeptide chain.

Hydrophobic (nonpolar) R groups avoid water and tend to cluster in the interior of the protein, away from the aqueous environment. Hydrophilic (polar) and ionic (charged) R groups interact favorably with water and are typically found on the protein’s surface. These tendencies drive the protein to fold into a specific three-dimensional shape, because each R group settles into the position that is most thermodynamically stable given its chemical properties.

The primary structure is the specific amino acid sequence of a polypeptide. This sequence determines how the chain folds, because the identity and order of R groups dictate which interactions form at each position. Therefore, the primary structure ultimately determines the secondary, tertiary, and quaternary structures — and thus the protein’s function.

Secondary structures form because hydrogen bonds develop at regular intervals between atoms of the polypeptide backbone. In an alpha-helix, backbone hydrogen bonds create a coiled shape, while in a beta-pleated sheet, hydrogen bonds between adjacent stretches of the backbone produce a flat, folded arrangement. These local folding patterns arise spontaneously from the repeating chemistry of the backbone.

The four interactions are hydrogen bonds between polar R groups, hydrophobic interactions among nonpolar R groups, ionic interactions between charged R groups, and disulfide bridges (covalent bonds between sulfur-containing cysteine R groups). Together, these interactions fold the polypeptide into its three-dimensional shape.

A change in pH alters the ionization state of charged and polar R groups, which disrupts the ionic interactions and hydrogen bonds that stabilize the protein’s tertiary (and potentially quaternary) structure. Without the correct three-dimensional shape, the protein can no longer bind its substrate or perform its biological role.

The hydrophilic amino acid would no longer participate in the hydrophobic interactions that hold the two subunits together. This would weaken the quaternary structure, potentially causing the subunits to dissociate or assemble incorrectly. Because hemoglobin requires all four subunits in the correct arrangement to carry oxygen efficiently, the mutation would likely reduce or eliminate hemoglobin’s oxygen-carrying function.