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Guide for Chapter 4. Protein secondary, tertiary, and quaternary structuresUnderstand and be able to draw a Ramachandran plot and recognize where common secondary structures are positioned on that plot.Understand the structure of the α-helix, the features and general amino acid preferences discussed in class, the bonds that hold it together, as well as where common helices would appear on a Ramachandran plot.- Right Handed a-helixo H-bond pattern Carbonyl of residue i and amide of residue i + 4o Few steric clasheso Glycine and Proline seen very little in secondary structuresUnderstand the concept of the helical wheel and how it is drawn for a helical peptidechain. Be able to draw a helical wheel given a peptide sequence and predict which face is buried inside and which face is likely to be on the surface of a protein.- Brown = facing protein interior- Blue = exposed to surfaceUnderstand the features of beta sheets (both parallel and anti-parallel) and the bonds that hold them together. Be able to draw short beta strands and know where they would fall on a Ramachandran plot. Be able to predict how they would fit into proteins (interior/exterior) based on amino acid sequence.- Beta Sheet- Keeps large and branch side chains far apart, minimizing steric clasho Parallel Non-linear H-bonds Weaker bonds than linearo Antiparallel Linear H-bonds Stronger than non-linearUnderstand the general nature of a hairpin turn including the importance of the amino acids proline and glycine in abrupt turns of a polypeptide chain.- Hairpin turnso Generally connect antiparallel beta sheetso Glycine is common in turns due to need for restrictive dihedral angleso Proline common in turns because its cis structure helps to induce changes in direction of main chainUnderstand the features of tertiary structure and quaternary structure discussed in class including the types of bonds that hold them together.- Tertiary Structureo 3D structure of a single, double, or triple bonded protein moleculeo Driven by non-specific hydrophobic interactionso Held together by dipole-dipole interactions, van der waals interactions, salt bridges, hydrogen bonds, and tight packing of side chains and cross links (disulfide bonds and metal centers)- Quaternary Structureo 3D structure of a multi-subunit protein and how the subunits fit togethero Stabilized by same forces as tertiary structureProtein Folding and DegradationDescribe how proteins are folded / denatured and the properties of common denaturants.- Protein Folding o Entropy driveno Chaperonins aid in the proper folding of misfolded proteins with exposed hydrophobic patcheso Proteins fold via a series of conformational changes that reduce their free energy and entropy until the native state is reached- Protein Denaturationo Can be caused by chemical means or energetic (heat)o Chaotropes are small molecules used to denature proteins Urea Guanidinium chlorideDescribe in detail a typical protein denaturation kinetic plot including the concept ofcooperativity in protein folding or unfolding.- Cooperative Unfoldingo When part of the structure is denatured, it destabilizes the remaining structureUnderstand the following terms in relation to protein folding: Native: The most optimal folded conformation of the proteinDenatured: Proteins in which the secondary and tertiary structure has been disrupted to create a random coilDesolvation Cost: Forming hydrogen bonds in the protein interior compensates for broken hydrogen bonds to water Hydrophobic Effect: The observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules Understand the role of hydrogen bonds and salt bridges (electrostatic interactions) in protein stability (difference in free energies between folded and unfolded states) and specificity (proper folding).- Hydrogen Bondso Key to defining protein structureo Necessary to keep protein stable but not major force in stability- Salt Bridgeso Interior salt bridges contribute little to stability and a lot to specificity o Exterior salt bridges contribute specificity for interaction with other proteins and ligandsUnderstand the meaning of Levinthal’s Paradox.- Levinthal's paradox is that finding the native folded state of a protein by a randomsearch among all possible configurations can take an enormously long time. Yet proteins can fold in seconds or less. Mathematical analysis of a simple model shows that a small and physically reasonable energy bias against locally unfavorable configurations, of the order of a few kT, can reduce Levinthal's time to a biologically significant size.- AKA Proteins do not fold by sequential random searchUnderstand the protein folding funnel and the meaning of a local minimum. Be able to draw a crudefunnel and label appropriately. Understand the potential problems that unfolded or misfolded proteins contribute to in the cell and the cellular conditions, which may lead to these problems.- Misfolded Protein Diseaseso Alzheimer’s Diseaseo Huntington’s Disease- Misfolded Prion Protein Diseaseso Scrapie in sheepo Wasting disease in deero Mad cow disease and creutzfedt-jakob disease in peopleUnderstand the function of chaperones in protein folding including the role of Chaperonin in preventing protein misfolding.- Molecular Chaperoneso Inhibit inappropriate interactions between potentially complementary surfaces and disrupt unsuitable liasons so as to facilitate more favorable associations- Chaperonino Aids in the proper folding of misfolded proteins with exposed hydrophobic patchesKnow the two major protein degradation pathways in the cell – lysosomal (10-20% of all proteins) and proteosomal (80-90% of all proteins). - Lysosomalo Digests Ingested materials Obsolete cell componentso Degrades macromolecules of all types Proteins Nucleic Acids Carbohydrates Lipids- Proteosomalo Proteins destined to be degraded are polyubiquitinatedo Polyubiquitinated proteins are recognized and degraded by 26S proteasomeRecognize major ways of protein delivery to lysosomes (phagocytosis, pinocytosis, receptor mediated endocytosis, and autophagy). - Phagocytosiso Cell “eating” of material- Pinocytosiso Cell “drinking”- Receptor Mediated Endocytosiso Clathrin-coated pits- Autophagyo “Self-eat” of old worn out organelleso Important in cell degradation during apoptosiso Important under starvation and to recycle entire organelles/aggregatesKnow the role of autophagy in


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OSU BIOCHEM 4511 - Guide for Chapter 4

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