Guide for Chapter 4 Protein secondary tertiary and quaternary structures Understand and be able to draw a Ramachandran plot and recognize where common secondary structures are positioned on that plot Understand the structure of the 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 helix o H bond pattern Carbonyl of residue i and amide of residue i 4 o Few steric clashes o Glycine and Proline seen very little in secondary structures Understand the concept of the helical wheel and how it is drawn for a helical peptide chain 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 surface Understand 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 clash o Parallel o Antiparallel Non linear H bonds Weaker bonds than linear Linear H bonds Stronger than non linear Understand 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 turns o Generally connect antiparallel beta sheets o Glycine is common in turns due to need for restrictive dihedral angles o Proline common in turns because its cis structure helps to induce changes in direction of main chain Understand the features of tertiary structure and quaternary structure discussed in class including the types of bonds that hold them together Tertiary Structure o 3D structure of a single double or triple bonded protein molecule o Driven by non specific hydrophobic interactions o 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 Structure o 3D structure of a multi subunit protein and how the subunits fit together o Stabilized by same forces as tertiary structure Protein Folding and Degradation Describe how proteins are folded denatured and the properties of common denaturants Protein Folding o Entropy driven o Chaperonins aid in the proper folding of misfolded proteins with exposed hydrophobic patches o Proteins fold via a series of conformational changes that reduce their free energy and entropy until the native state is reached Protein Denaturation o Can be caused by chemical means or energetic heat o Chaotropes are small molecules used to denature proteins Urea Guanidinium chloride Describe in detail a typical protein denaturation kinetic plot including the concept of cooperativity in protein folding or unfolding Cooperative Unfolding structure o When part of the structure is denatured it destabilizes the remaining Understand the following terms in relation to protein folding Native The most optimal folded conformation of the protein Denatured Proteins in which the secondary and tertiary structure has been disrupted to create a random coil Desolvation 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 Bonds Salt Bridges o Key to defining protein structure o Necessary to keep protein stable but not major force in stability o Interior salt bridges contribute little to stability and a lot to specificity o Exterior salt bridges contribute specificity for interaction with other proteins and ligands Understand the meaning of Levinthal s Paradox Levinthal s paradox is that finding the native folded state of a protein by a random search 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 search Understand the funnel and the minimum Be funnel and label protein folding meaning of a local able to draw a crude 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 Diseases o Alzheimer s Disease o Huntington s Disease Misfolded Prion Protein Diseases o Scrapie in sheep o Wasting disease in deer o Mad cow disease and creutzfedt jakob disease in people Understand the function of chaperones in protein folding including the role of Chaperonin in preventing protein misfolding Molecular Chaperones o Inhibit inappropriate interactions between potentially complementary surfaces and disrupt unsuitable liasons so as to facilitate more favorable associations Chaperonin o Aids in the proper folding of misfolded proteins with exposed hydrophobic patches Know the two major protein degradation pathways in the cell lysosomal 10 20 of all proteins and proteosomal 80 90 of all proteins Lysosomal o Digests Ingested materials Obsolete cell components o Degrades macromolecules of all types Proteins Nucleic Acids Carbohydrates Lipids Proteosomal o Proteins destined to be degraded are polyubiquitinated o Polyubiquitinated proteins are recognized and degraded by 26S proteasome Recognize major ways of protein delivery to lysosomes phagocytosis pinocytosis receptor mediated endocytosis and autophagy Phagocytosis Pinocytosis o Cell eating of material o Cell drinking Receptor Mediated Endocytosis o Clathrin coated pits Autophagy o Self eat of old worn out organelles o Important in cell degradation during apoptosis o Important under starvation and to recycle entire organelles aggregates Know the role of autophagy in degradation of old sick unneeded organelles and large protein aggregates including amyloids Recognize amyloids as