Essential Cell Biology 5th edition

160 CHAPTER 4 Protein Structure and Function
TABLE 4–2 HISTORICAL LANDMARKS IN OUR UNDERSTANDING OF PROTEINS
1838 The name “protein” (from the Greek proteios, “primary”) was suggested by Berzelius for the complex nitrogen-rich
substance found in the cells of all animals and plants
1819–1904 Most of the 20 common amino acids found in proteins were discovered
1864 Hoppe-Seyler crystallized, and named, the protein hemoglobin
1894 Fischer proposed a lock-and-key analogy for enzyme–substrate interactions
1897 Buchner and Buchner showed that cell-free extracts of yeast can break down sucrose to form carbon dioxide and
ethanol, thereby laying the foundations of enzymology
1926 Sumner crystallized urease in pure form, demonstrating that proteins could possess the catalytic activity of enzymes;
Svedberg developed the first analytical ultracentrifuge and used it to estimate the correct molecular weight of
hemoglobin
1933 Tiselius introduced electrophoresis for separating proteins in solution
1934 Bernal and Crowfoot presented the first detailed x-ray diffraction patterns of a protein, obtained from crystals of the
enzyme pepsin
1942 Martin and Synge developed chromatography, a technique now widely used to separate proteins
1951 Pauling and Corey proposed the structure of a helical conformation of a chain of amino acids—the α helix—and the
structure of the β sheet, both of which were later found in many proteins
1955 Sanger determined the order of amino acids in insulin, the first protein whose amino acid sequence was determined
1956 Ingram produced the first protein fingerprints, showing that the difference between sickle-cell hemoglobin and
normal hemoglobin is due to a change in a single amino acid (Movie 4.13)
1960 Kendrew described the first detailed three-dimensional structure of a protein (sperm whale myoglobin) to a
resolution of 0.2 nm, and Perutz proposed a lower-resolution structure for hemoglobin
1963 Monod, Jacob, and Changeux recognized that many enzymes are regulated through allosteric changes in their
conformation
1966 Phillips described the three-dimensional structure of lysozyme by x-ray crystallography, the first enzyme to be
analyzed in atomic detail
1973 Nomura reconstituted a functional bacterial ribosome from purified components
1975 Henderson and Unwin determined the first three-dimensional structure of a transmembrane protein
(bacteriorhodopsin), using a computer-based reconstruction from electron micrographs
1976 Neher and Sakmann developed patch-clamp recording to measure the activity of single ion-channel proteins
1984 Wüthrich used nuclear magnetic resonance (NMR) spectroscopy to solve the three-dimensional structure of a soluble
sperm protein
1988 Tanaka and Fenn separately developed methods for using mass spectrometry to analyze proteins and other
biological macromolecules
1996–2013 Mann, Aebersold, Yates, and others refine methods for using mass spectrometry to identify proteins in complex
mixtures, exploiting the availability of complete genome sequences
1975–2013 Frank, Dubochet, Henderson and others develop computer-based methods for single-particle cryoelectron
microscopy (cryo-EM), enabling determination of the structures of large protein complexes at atomic resolution
form of a gas. Accelerated by a powerful electric field, the peptide ions
then fly toward a detector; the time it takes them to arrive is related to
their mass and their charge. (The larger the peptide is, the more slowly it
moves; the more highly charged it is, the faster it moves.) The set of very
exact masses of the protein fragments produced by trypsin cleavage then
serves as a “fingerprint” that can be used to identify the protein—and its
corresponding gene—from publicly accessible databases (Figure 4−56).
This approach can even be applied to complex mixtures of proteins;
for example, starting with an extract containing all the proteins made
by yeast cells grown under a particular set of conditions. To obtain the
increased resolution required to distinguish individual proteins, such