Proteins, the working molecules of a cell, carry out the program of activities encoded by genes. This program requires the coordinated effort of many different types of proteins, which first evolved as rudimentary molecules that facilitated a limited number of chemical reactions. Gradually, many of these primitive proteins evolved into a wide array of enzymes capable of catalyzing an incredible range of intracellular and extracellular chemical reactions, with a speed and specificity that is nearly impossible to attain in a test tube. Other proteins acquired numerous structural, regulatory, and other functions. For a flavor of the various roles of proteins in today’s organisms, we can look to the yeast Saccharomyces cerevisiae, a simple unicellular eukaryote. The yeast genome is predicted to encode about 6225 proteins (see Table 7-3). On the basis of their sequences, 17 percent are estimated to be involved in metabolism, the synthesis or degradation of cell building blocks; 30 percent, in cellular organization and biogenesis of cell organelles and membranes; and 10 percent, in transporting molecules across membranes.
In this chapter, we will study how the structure of a protein gives rise to its function. The first section examines protein architecture: the structure and chemistry of amino acids, the linkage of amino acids to form a linear chain, and the forces that guide folding of the chain into higher orders of structure. In the next section, we learn about special proteins that aid in the folding of proteins, modifications that occur after the protein chain is synthesized, and mechanisms that degrade proteins. In the third section, we illustrate several key concepts in the functional design of proteins, using antibodies and enzymes as examples. A separate section is devoted to the general characteristics of membrane proteins, which reside in the lipid bilayer surrounding cells and organelles. These functionally diverse proteins play critical roles in transfer of molecules and information across the lipid bilayer and in cell-cell interactions; their structures and functions will be discussed in greater detail in later chapters. We finish the chapter by describing the most commonly used techniques in the biologist’s tool kit for isolating proteins and characterizing their properties. Our understanding of biology critically depends on how we can ask a question and test it experimentally.
Table 7-3. Estimated Total Number of Proteins and Number Predicted to Function in Certain Cell Processes in Microorganisms with Sequenced Genomes*
|M. genitalium||M. jannaschii||H. influenzae||E. coli||S. cerevisiae|
|Total genome length (kb)||580||1660||1830||4640||12,050|
|Total number of proteins†||470||1700||1700||4300||6200|
|Number of proteins with predicted functions in‡|
|Energy production and storage||40||130||140||240||175|
|DNA replication, repair, and recombination||40||90||110||120||175|
|Intracellular protein targeting and secretion||20||25||35||35||430|
* From left to right, the organisms are Mycoplasma genitalium, Methanococcus jannaschii, Haemophilus influenzae, Escherichia coli, and Saccharomyces cerevisiae. M. jannaschii is an archaen; M. genitalium, H. influenzae, and E. coli are bacteria; and S. cerevisiae is a single-celled eukaryote.
† Values are the approximate total number of proteins encoded in each genome. They are based on the number of long open reading frames, which can encode proteins containing 100 or more amino acids, plus shorter genes encoding characterized proteins.
‡ For each organism, only some of the proteins with predicted functions fall into the categories included in the table. The percentages of the estimated total number of proteins that have been assigned predicted functions vary among these organisms as follows: M. genitalium, 87%; M. jannaschii, 38%; H. influenzae, 83%; E. coli, 62%; and S. cerevisiae, 65%.
SOURCES: M. genitalium, C. M. Fraser et al., 1995, Science 270:397; M. jannaschii, C. J. Bult et al., 1996, Science 273:1058; H. influenzae.R. D. Fleischmann et al., 1995, Science 269:496; E. coli, F. R. Blattner et al., 1997, Science 277:1453; S. cerevisiae, A. Goffeau et al., 1996, Science 274:546. See also E. V. Koonin et al., 1997, Mol Microbiol. 25:619.