MCB 450 1st Edition Lecture 4Outline of Last Lecture I. Amino Acids & Their PropertiesII. Ionization of Amino AcidsIII. PeptidesIV. Secondary Structure of ProteinsOutline of Current LectureI. Tertiary and Quaternary Structure of Proteinsa. Globular Proteinsb. Motifs and Domainsc. Fibrous Proteinsd. CollagenII. Protein BioinformaticsIII. Protein Folding & DenaturationIV. Post-translational Modifications of ProteinsV. AmyloidosesCurrent LectureHow a sheet of mixed antiparallel and parallel beta-strands looks in a protein:-Each strand on the right is numbered and corresponds to the numbers on the lef-Need to be able to easily read structuresAntiparallel beta-sheet-To be able to make sharp turns in proteins need the right amino acids - Pro and Gly common-Loops typically found at the surface of a proteinoLoops would then be exposed to the cell surfaceAlpha-helices and beta-sheets-Plot will give a general area where structures are present-May be good to know approximate coordinates of these structuresTertiary StructureThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-Tertiary structure --- folding of a polypeptide in 3 dimensions-Motifs -- folds-Motifs are combined into domains Globular, fibrous, & membrane proteins-Know terms: globular, fibrous, membrane3-D Structure of globular proteins-In a protein some may be composed of all alpha or all beta, etc. Common structural motifs/folds in globular proteins-Examples of motifs -- helix-loop-helix, helix-turn-helix-Turn between parallel and alpha helix ofen contains the important amino acids that will do things for the cell like catalystsDomains-Polypeptide chain can have one domain or severalConstructing domains from motifs-Beta-barrel is present in the middle and then alpha helices on the outsideLoops ofen contain amino acids for catalytic activity-The larger 3D protein structure acts as a scaffold for other amino acids to do work -- like enzymes-Creates very specific binding pocket-Domains can have separate or combined functionsWhat about the side chains?- Does it matter where they are?oSidechains tend to be buried within the structureoThey create a very dense core that is hydrophobic that excludes wateroProteins tend to adopt very specific structures but proteins can have multiple conformationsQuaternary structure-Multisubunits -- might also be referred to as dimer or trimerFibrous proteins-Just exist, don't involve reactions, more for structural uses -- keratin, silkKeratin-Protofilaments make up protofibrils-The structure of silk explains why it is able to be so strongCollagen: a unique triple helical structure-Collagen is very important in mammals but is not one of the standard secondary structures-DIFFERENT from an alpha-helix-Steric repulsion stiffens the collagen strandHyroxyproline is made from Pro by an enzyme-If you have a Vitamin C deficiency -- this is why you end up with scurvy because your collagen is affected-Cure for scurvy was eventually discovered -- fresh fruitHow we detect 1 sequence relationships-Might use a protein sequence database to identify the function of protein that you discovered bylooking up similar protein sequences-Proteins cannot be more than 20% similar at the primary sequence level-But nevertheless they can still fold and look very similar to other proteinsProtein denaturation-Denaturation - destabilization of a protein oDisrupts the weak forces of the structure somehowoEx: cooking, heat-Graph:: how much of the protein is properly folded vs. temperature-Or denaturation can be caused by lower or high pHDenaturing agents-If you get rid of the urea -- the protein might be able to refold Model for protein folding-Molten glass is used as an analogy for the molten globule-We believe that each protein will follow a specific folding pathwayAlzheimer's disease-Patients with Alzheimer's will end up with a lot less brain