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Unformatted text preview: 3-1Cell and Molecular Biology (Biol. Chem. 410A)Lecture #3Harry R. Matthews, Ph.D.September 30, 1996Hierarchies of Protein StructureClinical correlations:•aspartame•Hemoglobin Riverdale-Bronx•constitutively active oncogenesLearning objectives:•the peptide bond•principles of peptide folding•primary, secondary, tertiary, quaternary structures•structural motifs and domains•functional motifs and domainsOptional reading:•Stryer IV:Chapter 2•Alberts et al.:3rd Ed., Chapter 3, pp. 111-123.Importance of Structure.The last lecture discussed the chemical groups and the bonds between them in proteins. This is only half the story since each protein gener-cytoplasmextra-cellular fluidV-erbBEGF receptorFigure 3-2. An oncogene. V-erbB is the product of an oncogene (causes cancer). It is formed by muta-tion of the gene for the EGF receptor which removes the binding domain for EGF. V-erbB signals the cell to grow whether or not EGF is present.Figure 3-1. Aspartame. This dipeptide is widely used as an artificial sweetener—Nutrasweet®—and people with phenylketonuria need to be aware of its phenylalanine content.3-2ally takes up a spe-cific shape or folding pattern in the body. It is this specific shape, or structure, that brings together the parts of the pro-tein that are needed for its function. Al-though proteins fold into complex and unique shapes, there are several common recurring structures that help us to un-derstand how pro-teins fold and how this affects their function. That is the subject of this lecture.Proteins that cause disease may do so by having an incorrect structure, as we will see later with an inborn error in hemoglobin where a small amino acid, glycine, is replaced by a large amino acid that cannot fit into the small space available within the normal hemoglobin structure. In this case, the struc-ture of hemoglobin is destabilized and anemia results. Rotation About α Carbon.Peptides and proteins can form very complex shapes by rotation of the back-bone about the single bonds on either side of the α-carbon atom of each residue. The angles of rotation are called ψ (psi) and φ (phi) and ψand φ may have different values for each α-carbon atom.Amino Acid Sequence Determines Folding Pattern.A polypeptide chain will form a number of re-peating structures but the stability of these structures is strongly dependent on the side-chains. The actual folding pattern is thus fixed by the environment of the protein and its amino acid sequence. The folding of the main chain can be described in terms of the two angles ψ and φ for each peptide bond....
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- Spring '03