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Unformatted text preview: 9. Protein Folding The structure of proteins is described on several scales. The primary structure is the amino acid sequence which is coded in the gene for the protein. Secondary structure describes the chain forming alpha helices, beta sheets and loops. Tertiary structure describes how the helices, sheets and loops are assembled into a working unit. Review these concepts from the lecture on proteins. Linus Pauling predicted the alpha helix secondary structure in 1948. His conjec- tured structure was based on his knowledge of covalent bonds and hydrogen bonds, and geometric reasoning using a piece of paper that he folded. Here is a copy of his sketch on the unfolded sheet of paper. He asked himself how the long chain of the protein backbone could be arranged so that the oxygens and the hydrogens on the backbone form a hydrogen bond. His folded paper (figure 1) brought the points A and B close together and created a hydrogen bond between the negatively charged oxygen and the positively charged hydrogen. The hydrogen bond completed a ring consisting of 13 atoms and showed a helix with 3.6 residues per turn. Structures of proteins were later obtained by crystallography, confirming Paulings conjecture. Figure 1. Paper folded by Linus Pauling in 1948 to predict the structure of the alpha helix. All Pauling needed to make his discovery was the sequence of atoms and a knowledge about hydrogen bonds created by the electric force between the positively charged H bonded to N and the negatively charged. O bonded to C. This raises the question of whether protein structures can be determined from just the sequence of amino acids and all the forces between the atoms. Possibly with powerful computers and a knowledge of all the forces between atoms in a protein, the structure can be determined without experiments in the same way that Pauling did. 9.1. Anfinsens hypothesis. The above question is related to Anfinsens hypoth- esis, one of the basic tenants of structural genomics. It states that information determining the structure of a protein resides in the chemistry of its amino acid sequence. For example, it says that the amino acid sequence of Bacteriorhodopsin: TGRPEWIWLALGTALMGLGTLYFLVKGMGVSDPDAKKFYAITT 1 2 LVPAIAFTMYLSMLLGYGLTMVPFGGEQNPIYWARYADWLFTT PLLLLDLALLVDADQGTILALVGADGIMIGTGLVGALTKVYSY RFVWWAISTAAMLYILYVLFFGFTSKAESMRPEVASTFKVLRN VTVVLWSAYPVVWLIGSEGAGIVPLNIETLLFMVLDVSAKVGF GLILLRSRAIFGE determines the structure shown in figure 2 that we find in the pdb file 1E0P. Figure 2. The structure of the protein Bacteriorhodopsin The structure of the functional protein is called the native state . The process by which a protein folds into this structure from an extended chain is called folding (figure 3)....
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This note was uploaded on 01/15/2012 for the course MAP 5485 taught by Professor Staff during the Fall '11 term at FSU.
- Fall '11