When we look at a cell through a microscope or analyze its electrical or biochemical activity, we are, in essence, observing proteins. Proteins constitute most of a cell’s dry mass. They are not only the cell’s building blocks; they also execute the majority of the cell’s functions. Thus, proteins that are enzymes provide the intricate molecular surfaces inside a cell that catalyze its many chemical reactions. Proteins embedded in the plasma membrane form channels and pumps that control the passage of small molecules into and out of the cell. Other proteins carry messages from one cell to another, or act as signal integrators that relay sets of signals inward from the plasma membrane to the cell nucleus. Yet others serve as tiny molecular machines with moving parts: kinesin, for example, propels organelles through the cytoplasm; topoisomerase can untangle knotted DNA molecules. Other specialized proteins act as antibodies, toxins, hormones, antifreeze molecules, elastic fibers, ropes, or sources of luminescence. Before we can hope to understand how genes work, how muscles contract, how nerves conduct electricity, how embryos develop, or how our bodies function, we must attain a deep understanding of proteins.
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 we realize that the structure and chemistry of each protein has been developed and fine-tuned over billions of years of evolutionary history. The theoretical calculations of population geneticists reveal that, over evolutionary time periods, a surprisingly small selective advantage is enough to cause a randomly altered protein sequence to spread through a population of organisms. Yet, even to experts, the remarkable versatility of proteins can seem truly amazing.
In this section, we consider how the location of each amino acid in the long string of amino acids that forms a protein determines its three-dimensional shape. Later in the chapter, we 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.
The Shape of a Protein Is Specified by Its Amino Acid Sequence
There are 20 different of amino acids in proteins that are coded for directly in an organism’s DNA, each with different chemical properties. A protein molecule is made from a long unbranched chain of these amino acids, each linked to its neighbor through a covalent peptide bond. Proteins are therefore also known as polypeptides. Each type of protein has a unique sequence of amino acids, and there are many thousands of different proteins in a cell.
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 that give each amino acid its unique properties: the 20 different amino acid side chains (Figure 3–1). Some of these side chains are nonpolar and hydrophobic
Figure 3–1 The 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 that makes each protein distinct. The two ends of a polypeptide chain are chemically different: the end carrying the free amino group (NH3+, also written NH2) is the amino terminus, or N-terminus, and that carrying the free carboxyl group (COO–, also written COOH) is the carboxyl terminus or C-terminus. The amino acid sequence of a protein is always presented in the N-to-C direction, reading from left  to right.
(“water-fearing”), others are negatively or positively charged, some readily form covalent bonds, and so on. Panel 3–1 (pp. 112–113) shows their atomic structures and Figure 3–2 lists their abbreviations.