Scientists distinguish four levels of organization in the structure of a protein. The amino acid sequence is known as the primary structure. Stretches of polypeptide chain that form α helices and β sheets constitute the protein’s secondary structure. The full three-dimensional organization of a polypeptide chain is sometimes referred to as the tertiary structure, and if a particular protein molecule is formed as a complex of more than one polypeptide chain, the complete structure is designated as the quaternary structure.
Studies of the conformation, function, and evolution of proteins have also revealed the central importance of a unit of organization distinct from these four. This is the protein domain, a substructure produced by any contiguous part of a polypeptide chain that can fold independently of the rest of the protein into a compact, stable structure. A domain usually contains between 40 and 350 amino acids, and it is the modular unit from which many larger proteins are constructed.
The different domains of a protein are often associated with different functions. Figure 3–10 shows an example—the Src protein kinase, which functions in signaling pathways inside vertebrate cells (Src is pronounced “sarc”). This protein stripe of hydrophobic helices wrap around each other to minimize exposure of hydrophobic amino acid side chains to aqueous environment 0.5 nm
Figure 3–8 Two types of β sheet structures. (A) An antiparallel β sheet (see Figure 3–7C). (B) A parallel β sheet. Both of these structures are common in proteins.
Figure 3–9 a coiled-coil. (A) A single α helix, with successive amino acid side chains labeled in a sevenfold sequence, “abcdefg” (from bottom to top). Amino acids “a” and “d” in such a sequence lie close together on the cylinder surface, forming a “stripe” (green) that winds slowly around the α helix. Proteins that form coiled-coils typically have nonpolar amino acids at positions “a” and “d.” Consequently, as shown in (B), the two α helices can wrap around each other with the nonpolar side chains of one α helix interacting with the nonpolar side chains of the other. (C) The atomic structure of a coiled-coil determined by x-ray crystallography. The alpha helical backbone is shown in red and the nonpolar side chains in green, while the more hydrophilic amino acid side chains, shown in gray, are left exposed to the aqueous environment (Movie 3.4). (PDB code: 3NMD.) is considered to have three domains: the SH2 and SH3 domains have regulatory roles, while the C-terminal domain is responsible for the kinase catalytic activity. Later in the chapter, we shall return to this protein, in order to explain how proteins can form molecular switches that transmit information throughout cells.
Figure 3–11 presents ribbon models of three differently organized protein domains. As these examples illustrate, the central core of a domain can be constructed from α helices, from β sheets, or from various combinations of these two fundamental folding elements.
The smallest protein molecules contain only a single domain, whereas larger proteins can contain several dozen domains, often connected to each other by short, relatively unstructured lengths of polypeptide chain that can act as flexible hinges between domains.
Few of the Many Possible Polypeptide Chains Will Be Useful  to Cells
Since each of the 20 amino acids is chemically distinct and each can, in principle, occur at any position in a protein chain, there are 20 × 20 × 20 × 20 = 160,000 different possible polypeptide chains four amino acids long, or 20n different possible polypeptide chains n amino acids long. For a typical protein length of about 300 amino acids, a cell could theoretically make more than 10390 (20300) different polypeptide chains. This is such an enormous number that to produce just one molecule of each kind would require many more atoms than exist in the universe.
Only a very small fraction of this vast set of conceivable polypeptide chains would adopt a stable three-dimensional conformation—by some estimates, less