Chapter 2: Protein Composition & Structure

The foundation of protein architecture is the linear polymer of amino acids, which are chiral, L-isomer building blocks classified by their side chains into hydrophobic, polar, positively charged, and negatively charged groups,. These amino acids are linked by peptide bonds, which exhibit partial double-bond character and planarity, restricting conformational flexibility to rotation around phi and psi torsion angles as visualized on Ramachandran plots,. The text details the hierarchy of protein structure, beginning with the primary amino acid sequence determined by genetic information, which dictates the higher-order folding patterns. Secondary structure arises from hydrogen bonding in the polypeptide backbone, forming periodic motifs such as the alpha helix, stabilized by intrachain bonds, and the beta sheet, composed of parallel or antiparallel strands, as well as non-repetitive loops and turns that reverse chain direction,. Specialized fibrous proteins like alpha-keratin, which forms coiled coils, and collagen, a triple helix stabilized by glycine and hydroxyproline, illustrate how structure dictates mechanical properties in tissues,. The discussion extends to tertiary structure, where water-soluble proteins fold into compact, asymmetric globular shapes driven by the hydrophobic effect, burying nonpolar residues in the interior while exposing polar groups to the aqueous environment, a pattern inverted in membrane proteins like porins,. Quaternary structure is described through the assembly of multiple polypeptide subunits, such as the tetrameric arrangement of hemoglobin. The chapter also covers the thermodynamics of protein folding, highlighting Anfinsen's experiments with ribonuclease which proved that sequence specifies conformation, and discussing the cooperative nature of folding via nucleation-condensation models to resolve Levinthal's paradox,. Finally, the text explores deviations from the central dogma, including intrinsically unstructured and metamorphic proteins, post-translational modifications like phosphorylation and cleavage, and the pathological consequences of protein misfolding, such as the formation of amyloid fibrils and prions in neurodegenerative diseases like Alzheimer's and transmissible spongiform encephalopathies.