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PROTEIN STRUCTURE (Donaldson, March 10,2003) What are we trying to learn about genes and their proteins: Predict function for unknown protein by comparison to known proteins. Determine the relationship of proteins to each other evolutionary history. Alignment of amino acid sequences suggests common functions. Three dimensional structure of an unknown protein may give clues to function. Compare with 3D structures of known proteins. Evolutionary tree showing how the globin protein family arose, starting from the most primitive oxygenbinding proteins, leghemoglobins, in plants. Molecular Cell Biology. 4th ed. Lodish, : W H Freeman & Co; c2000. Figure 5.23 The quaternary structure of proteins Evolutionary of like globin chains that carry oxygen in the blood of animals. A relatively recent gene duplication of the -chain gene produced G and A, which are fetal -like chains of identical function. The location of the globin genes in the human genome is shown at the top. Molecular Biology of the Cell. 3rd ed. Alberts, Garland Publishing; c1994 A comparison of the structure of one-chain and four-chain globins. The four-chain globin shown is hemoglobin, which is a complex of two - and two globin chains. The one-chain globin in some primitive vertebrates forms a dimer that dissociates when it binds oxygen, representing an intermediate in the evolution of the four-chain globin. Molecular Biology of the Cell. 3rd ed. Alberts, Garland Publishing; c1994 Protein Structures The features and forces of proteins structure Primary sequence of amino acids Secondary interactions form coils and sheets Tertiary interactions cause coils and sheets to fold upon each other. Quaternary interactions between separate protein molecules result in multi-subunit structures. Techniques used to determine protein structure. Hemoglobin will be the main example What are the forces between amino acid residues in a protein? Ionic interactions between oppositely charged residues can pull them together. Hydrogen Bonds - Hydrogens are partially positively charged, are attracted to partially negative oxygens. (weaker) van Der Waals - hydrophobic residues become attractive to each other when forced together by exclusion from the aqueous surroundings. (weakest) Figure 5.22 Examples of interactions contributing to the tertiary structure of a protein Figure 5.24 Review: the four levels of protein structure Figure 5.26 A chaperonin in action Protein structures are determined by two techniques X-ray diffraction of pure protein crystal Nuclear Magnetic Resonance of smaller protein molecule Usually in solution Figure 5.27 X-ray crystallography 1864 Hoppe-Seyler crystallized, and named, the protein hemoglobin. 1895 Rntgen observed that a new form of penetrating radiation, which he named xrays, was produced when cathode rays (electrons) hit a metal target. 1935 Patterson developed an analytical method for determining interatomic spacings from xray data. 1941 Astbury obtained the first x-ray diffraction pattern of DNA. 1912 W.L. Bragg proposed a simple relationship between an x-ray diffraction pattern and the arrangement of atoms in a crystal that produced the pattern. 1951 Pauling and Corey proposed the structure of a helical conformation of a chain of L-amino acids - the a-helix - and the structure of the b-sheet, both of which were later found in many proteins. 1926 Summer obtained crystals of the enzyme urease from extracts of jack beans and demonstrated that proteins possess catalytic activity. 1953 Watson and Crick proposed the double-helix model of DNA, based on x-ray diffraction patterns obtained by Franklin and Wilkins. 1931 Pauling published his first essays on "The Nature of the Chemical Bond," detailing the rules of covalent bonding. 1954 Perutz and colleagues developed heavy-atom methods to solve the phase problem in protein crystallography. 1934 Bernal and Crowfoot presented the first detailed x-ray diffraction patterns of a protein obtained from crystals of the enzyme pepsin. 1960 Kendrew described the first detailed structure of a protein (sperm whale myoglobin) to a resolution of 0.2 nm, and Perutz proposed a lower-resolution structure of the larger protein hemoglobin. Figure 6.14 The induced fit between an enzyme and its substrate