CLASSES OF PROTEIN STRUCTURE 1.Primary protein structure • Together, peptide bonds and amino acids form a polypeptide chain (aka a protein). • The primary structure of a protein determines its secondary and tertiary structures. As a clinical correlate, in sickle cell anemia, a single substitution of an amino acid in the primary structure of the protein results in a structural defect in hemoglobin. 2.Secondary protein structure • Two basic forms: alpha-helices and beta-sheets • Hydrogen bond interactions within the alpha-helix and beta-sheet provide the stability of secondary structure of proteins. Alpha-helices • Low energy conformations that enable higher-order packing of proteins. • Large or charged amino acid groups (such as proline) can disable the alpha helix conformation by manually disrupting the hydrogen bond interactions. Beta-pleated sheets • More structurally diverse than alpha helices and thus facilitate more diverse protein functions. • Create stable, diverse structures within a protein to allow higher order functions. • There are two notable ways in which the beta-pleated sheet can exist: - Parallel — the peptide chain advances in a single direction. - Anti-parallel — the peptide chain advances in two opposite directions.As a clinical correlate, prions are pathogenic, transmissible agents, which cause conversion from an alpha-helical form to a beta-sheet-rich conformer. Prions accumulate in the brain and cause a variety of spongiform encephalopathies, such as “mad cow disease”.3.Tertiary protein structure • Is the protein’s three-dimensional shape (its "native conformation") and the function of a protein is dependent on this three-dimensional globular structure. • Primarily comprises alpha helices and beta sheets. 4.Quaternary protein structure • Forms through the interaction of 2 or more separate proteins. • Comprises multiple polypeptide chains and occurs in certain protein types, called functional multimeric proteins.Tertiary & Quaternary protein bonding • The most significant stabilizer of tertiary and quaternary protein structures are hydrophobic interactions. • The following additional forces stabilize these structures: - Hydrophilic interactions. - Electrostatic interactions. - Hydrogen bonds between side chains. - Strong disulfide bonds.