From a chemical point of view, proteins are by far the most structurally complex and functionally sophisticated molecules known. This is perhaps not surprising, once one realizes that the structure and chemistry of each protein has been developed and fine-tuned over billions of years of evolutionary history. We start this chapter by considering how the location of each amino acid in the long string of amino acids that forms a protein determines its three-dimensional shape. We will then use this understanding of protein structure at the atomic level to describe how the precise shape of each protein molecule determines its function in a cell.
Go to:The Shape of a Protein Is Specified by Its Amino Acid Sequence
Recall from Chapter 2 that there are 20 types of amino acids in proteins, each with different chemical properties. A protein molecule is made from a long chain of these amino acids, each linked to its neighbor through a covalent peptide bond (Figure 3-1). Proteins are therefore also known as polypeptides. Each type of protein has a unique sequence of amino acids, exactly the same from one molecule to the next. Many thousands of different proteins are known, each with its own particular amino acid sequence.
Figure 3-1
A peptide bond. This covalent bond forms when the carbon atom from the carboxyl group of one amino acid shares electrons with the nitrogen atom (blue) from the amino group of a second amino acid. As indicated, a molecule of water is lost in this condensation (more...)
The repeating sequence of atoms along the core of the polypeptide chain is referred to as the polypeptide backbone. Attached to this repetitive chain are those portions of the amino acids that are not involved in making a peptide bond and which give each amino acid its unique properties: the 20 different amino acid side chains (Figure 3-2). Some of these side chains are nonpolar and hydrophobic (“water-fearing”), others are negatively or positively charged, some are reactive, and so on. Their atomic structures are presented in Panel 3-1, and a brief list with abbreviations is provided i
The structural components of a protein. A protein consists of a polypeptide backbone with attached side chains. Each type of protein differs in its sequence and number of amino acids; therefore, it is the sequence of the chemically different side chains (more...)
Panel 3-1
The 20 Amino Acids Found in Proteins.
Figure 3-3
The 20 amino acids found in proteins. Both three-letter and one-letter abbreviations are listed. As shown, there are equal numbers of polar and nonpolar side chains. For their atomic structures, see Panel 3-1 (pp. 132–133).
As discussed in Chapter 2, atoms behave almost as if they were hard spheres with a definite radius (their van der Waals radius). The requirement that no two atoms overlap limits greatly the possible bond angles in a polypeptide chain (Figure 3-4). This constraint and other steric interactions severely restrict the variety of three-dimensional arrangements of atoms (or conformations) that are possible. Nevertheless, a long flexible chain, such as a protein, can still fold in an enormous number of ways.
Figure 3-4
Steric limitations on the bond angles in a polypeptide chain. (A) Each amino acid contributes three bonds (red) to the backbone of the chain. The peptide bond is planar (gray shading) and does not permit rotation. By contrast, rotation can occur about (more...)
The folding of a protein chain is, however, further constrained by many different sets of weak noncovalent bonds that form between one part of the chain and another. These involve atoms in the polypeptide backbone, as well as atoms in the amino acid side chains. The weak bonds are of three types: hydrogen bonds, ionic bonds, and van der Waals attractions, as explained in Chapter 2 (see p. 57). Individual noncovalent bonds are 30–300 times weaker than the typical covalent bonds that create biological molecules. But many weak bonds can act in parallel to hold two regions of a polypeptide chain tightly together. The stability of each folded shape is therefore determined by the combined strength of large numbers of such noncovalent bonds (Figure 3-5).
