combinations of protein domains, with the result that there are nearly twice as many combinations of domains found in human proteins as in a worm or a fly. Thus, for example, the trypsinlike serine protease domain is linked to at least 18 other types of protein domains in human proteins, whereas it is found covalently joined to only 5 different domains in the worm. This extra variety in our proteins greatly increases the range of protein–protein interactions possible (see Figure 3–79), but how it contributes to making us human is not known.
The complexity of living organisms is staggering, and it is quite sobering to note that we currently lack even the tiniest hint of what the function might be for more than 10,000 of the proteins that have thus far been identified through examining the human genome. There are certainly enormous challenges ahead for the next generation of cell biologists, with no shortage of fascinating mysteries to solve.
The same weak noncovalent bonds that enable a protein chain to fold into a specific conformation also allow proteins to bind to each other to produce larger structures in the cell. Any region of a protein’s surface that can interact with another molecule through sets of noncovalent bonds is called a binding site. A protein can contain binding sites for various large and small molecules. If a binding site recognizes the surface of a second protein, the tight binding of two folded polypeptide chains at this site creates a larger protein molecule with a precisely defined geometry. Each polypeptide chain in such a protein is called a protein subunit.
In the simplest case, two identical folded polypeptide chains bind to each other in a “head-to-head” arrangement, forming a symmetric complex of two protein subunits (a dimer) held together by interactions between two identical binding sites. The Cro repressor protein—a viral gene regulatory protein that binds to DNA to turn specific viral genes off in an infected bacterial cell—provides an example (Figure 3–18). Cells contain many other types of symmetric protein complexes, formed from multiple copies of a single polypeptide chain (for example, see Figure 3–20 below).
Many of the proteins in cells contain two or more types of polypeptide chains. Hemoglobin, the protein that carries oxygen in red blood cells, contains two identical α-globin subunits and two identical β-globin subunits, symmetrically arranged (Figure 3–19). Such multisubunit proteins are very common in cells, and they can be very large (Movie 3.6).
Most of the proteins that we have discussed so far are globular proteins, in which the polypeptide chain folds up into a compact shape like a ball with an irregular surface. Some of these protein molecules can nevertheless assemble to form filaments that may span the entire length of a cell. Most simply, a long chain of identical protein molecules can be constructed if each molecule has a binding
Figure 3–18 Two identical protein subunits binding together to form a symmetric protein dimer. The Cro repressor protein from bacteriophage lambda binds to DNA to turn off a specific subset of viral genes. Its two identical subunits bind head-to-head, held together by a combination of hydrophobic forces (blue) and a set of hydrogen bonds (yellow region). (Adapted from D.H. Ohlendorf,
D.E. Tronrud and B.W. Matthews, J. Mol. Biol. 280:129–136, 1998. With permission from Academic Press.)
Figure 3–19 a protein formed as a symmetric assembly using two each of two different subunits. Hemoglobin is an abundant protein in red blood cells that contains two copies of α-globin (green) and two copies of β-globin (blue). Each of these four polypeptide chains contains a heme molecule (red), which is the site that binds oxygen (O2). Thus, each molecule of hemoglobin in the blood carries four molecules of oxygen. (PDB code: 2DHB.)