Recitation 3 Protein polymerization structure and conventional depictions in biology Goals 1 Review in class concepts of protein structure and folding 2 Learn the multiple ways that proteins are depicted in scientific literature and your textbook You have probably heard of prion proteins the culprits behind the Mad Cow disease scare of the mid 90 s Prion proteins are convenient for discussion of protein structure and folding because they are relatively small for proteins Also the diseases they cause are unusual in that they are infectious yet not caused by the usual suspects viruses bacteria fungi or parasites Introduction Prion proteins PrP in their noninfectious form referred to as PrPC for cellular form are useful members of cellular society We re not entirely sure what function they perform but the latest thought is that they aid in the health and connectivity of neurons in the brain and the maintenance and repair of the myelin sheaths that insulate neurons Disease arises when the victim eats the infectious form of the protein called PrP Sc It s the same protein but it has been somehow warped into a zombie version of itself Like a zombie it no longer serves any cellular function Worse it shuffles around finding others of its kind latching onto them and turning them into misfolded zombies like itself And like zombies it s hard to kill the normal cellular machinery that degrades misfolded damaged or malformed proteins cannot destroy it The victim s brain fills with big clumps of the useless prions and ultimately big spongy holes see image on right Prions are not destroyed by the heat of cooking or by the low pH of gastric juices Kuru is one example of a prion disease unsteady gait slurred speech muscle tremors uncontrollable laughter and eventually death Ironically the zombie protein is passed on primarily through the consumption of diseased brain tissue Let s take a look at the prion protein and how such proteins are presented in the literature Read the document and answer the questions about prion proteins on the attached workskeet You only need to turn in one worksheet per group Prion Primary structure The primary sequence1 of the full prion protein is 253 amino acids long Amino acid numbering begins at the N terminal end Primary sequences are always depicted using single letter abbreviations so I require students to memorize the letters If you print out the full color version of this document you will see that the colors correspond to the four groups of amino acids green for nonpolar aqua for polar red for acidic and purple for basic Primary sequence alignment Often it is useful to compare sequences of the same protein between species There are online tools to do this Below is a comparison between five vertebrate species 2 The highlighted regions amino acids 98 157 show stretches of amino acids that are mostly identical between all of them The prion protein was present in the common ancestor of all of these vertebrates and the important regions have not changed much over the millenia Protein functional domain diagram It s also common to see the primary structure depicted as a diagram depicting information about the functions of the protein and areas of particular interest The diagram below 3 shows several relevant features that you don t have to know but I want to draw your attention to two of them The disulfide bond between amino acids 179 and 214 and the HC hydrophobic core region between 111 134 1 http www diseasemotifs co uk prion prprotein html Pietropaolo et al 2009 ChemPhysChem 10 9 10 1500 10 3 Aguzzi Heikenwalder 2006 Nat Rev Microbio 4 765 775 2 Prion secondary and tertiary structure Ribbon Diagram The diagram below is a very common way to illustrate the three dimensional shape of a protein Such diagrams are often found online as an animation to allow the viewer to rotate the molecule If you refer to the full color version of this document you can see that the alpha helices are rendered in green the beta sheets in red and the single disulfide bond in yellow This diagram also illustrates the distinction between the PrpC form normal left and the PrPSc form zombified abnormal form right You might not be able to infer the functions tehy perform but they are very clearly different 3D stuctures and we all know that structure relates to function Process Model diagrams Many of the diagrams in your book are simple depictions of a process or order of events The diagram below4 depicts how the abnormal prion proteins interact with normal endogenous already present in body PrPC proteins Note that in these types of diagrams the proteins are just depicted as simple blobs I threw this diagram to make the point that you will be seeing many different kinds of diagrams in this class that depict blobs and arrows Make sure you can distinguish between a model diagram like this one a metabolic pathway diagram an electron transport chain and a signal processing diagram It s not entirely clear in the literature yet 1 where the misfolded PrPSc proteins originally came from and 2 how they convert PrPC to a misfolded form 4 http www vce bioninja com au aos 2 detecting and respond defence against disease pathogens html Chart of Amino Acids organized by properties