3.1 Hierarchical Structure of Proteins

In many proteins, the polymer chain folds into a distinct three-dimensional shape that is stabilized primarily by noncovalent interactions between regions in the linear sequence of amino acids. A key concept in understanding how proteins work is that function is often derived from three-dimensional structure, and three-dimensional structure is determined by both a protein’s amino acid sequence and intramolecular noncovalent interactions. The principles relating biological structure and function were initially formulated by the biologists Johann von Goethe (1749–1832), Ernst Haeckel (1834–1919), and D’Arcy Thompson (1860–1948), whose work has been widely influential in biology and beyond. Indeed, their ideas greatly influenced the school of “organic” architecture pioneered in the early twentieth century that is epitomized by the dicta “form follows function” (Louis Sullivan) and “form is function” (Frank Lloyd Wright). Here we consider the architecture of proteins at four levels of organization: primary, secondary, tertiary, and quaternary (Figure 3-2).

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FIGURE 3-2 Four levels of protein hierarchy. (a) The linear sequence of amino acids linked together by peptide bonds is the primary structure. (b) Folding of the polypeptide chain into local α helices or β sheets represents secondary structure. (c) Secondary structural elements, together with various loops and turns in a single polypeptide chain, pack into a larger, independently stable tertiary structure, which may include distinct domains. (d) Some proteins consist of more than one polypeptide associated together in a quaternary structure.