Most proteins fold up into a single stable conformation. However, this conformation changes slightly when the protein interacts with other molecules in the cell. This change in shape is often crucial to the function of the protein, as we see later.
Although a protein chain can fold into its correct conformation without outside help, in a living cell special proteins called molecular chaperones often assist in protein folding. Molecular chaperones bind to partly folded polypeptide chains and help them progress along the most energetically favorable folding pathway. In the crowded conditions of the cytoplasm, chaperones are required to prevent the temporarily exposed hydrophobic regions in newly synthesized protein chains from associating with each other to form protein aggregates (see p. 355). However, the final three-dimensional shape of the protein is still specified by its amino acid sequence: chaperones simply make reaching the folded state more reliable.
Figure 3–5 How a protein folds into a compact conformation. The polar amino acid side chains tend to lie on the outside of the protein, where they can interact with water; the nonpolar amino acid side chains are buried on the inside forming a tightly packed hydrophobic core of atoms that are hidden from water. In this schematic drawing, the protein contains only about  35 amino acids.
Figure 3–6 Four representations describing the structure of a small protein domain. Constructed from a string of 100 amino acids, the SH2 domain is part of many different proteins (see, for example, Figure 3–61). Here, the structure of the  SH2 domain is displayed as (A) a polypeptide backbone model, (B) a ribbon model, (C) a wire model that includes the amino acid side chains, and (D) a space-filling model (Movie 3.1). These images are colored in a way that allows the polypeptide chain to be followed from its N-terminus (purple) to its C-terminus (red) (PDB code: 1SHA).
Proteins come in a wide variety of shapes, and most are between 50 and 2000 amino acids long. Large proteins usually consist of several distinct protein domains—structural units that fold more or less independently of each other, as we discuss below. The structure of even a small domain is complex, and for clarity, several different representations are conventionally used, each of which emphasizes distinct features. As an example, Figure 3–6 presents four representations of a protein domain called SH2, a structure present in many different proteins in eukaryotic cells and involved in cell signaling (see Figure 15–46).
Descriptions of protein structures are aided by the fact that proteins are built up from combinations of several common structural motifs, as we discuss next.
The α Helix and the β Sheet Are Common Folding Patterns
When we compare the three-dimensional structures of many different protein molecules, it becomes clear that, although the overall conformation of each protein is unique, two regular folding patterns are often found within them. Both patterns were discovered more than 60 years ago from studies of hair and silk. The first folding pattern to be discovered, called the α helix, was found in the protein α-keratin, which is abundant in skin and its derivatives—such as hair, nails, and horns. Within a year of the discovery of the α helix, a second folded structure, called a β sheet, was found in the protein fibroin, the major constituent of silk. These two patterns are particularly common because they result from hydrogen-bonding between the N–H and C=O groups in the polypeptide backbone, without involving the side chains of the amino acids. Thus, although incompatible with some amino acid side chains, many different amino acid sequences can form them. In each case, the protein chain adopts a regular, repeating conformation. Figure 3–7 illustrates the detailed structures of these two important conformations, which in ribbon models of proteins are represented by a helical ribbon and by a set of aligned arrows, respectively.
0.54 nm
R R R R R R R R R R RR R R R H-bond hydrogen amino acid side chain nitrogen carbon carbon peptide bond oxygen (C) (D) 0.7 nm