BICH 410 1st Edition Lecture 24 Outline of Last Lecture I Membrane Structure Current Lecture Test info know how mechanisms work that were gone over in class should be able to compare membrane protein characteristics with globular and fibrous proteins Proteins found on cytoplasmic side of membrane Thioester connects to membrane via cysteine N myristotyltransferase link is non reversible and is a target for anti parastitic drugs Palmitoyl thioesterase catalyzes reversible additions where protein participate in transmembrane signaling GPI phospholipid such as phosphotidyl inositol modified sugar with glycosylation and protein attached o Always on outside of cell extracellularly located Lipid asymmetry can have protein only on inside or only on outside same with lipids o More sphigomyeline on outside less inside Lipid asymmetry phospholipids are synthesized on or near interior of membrane o ATP dependent flippase outer to inner o ATP dependent floppase inner to outer Both nonequilibrium distribution of phospholipids o Bidirectional scramlase inner to outer in order to produce equilibrium distb Temperature dependence of fluidity of a bilater o Below transition temp bilayer becomes gel like solid solid order state o Above transition temp bilayer is liquid crystal liquid order state o Transition temp depends on chain length and degree of sat Increase in Carbon increase in melting point Increase in double bonds decrease in melting temp Cholesterol broadens temp range of phase transition o As temp increases increase in composition of long chain saturation fatty acids o As temp decreases increase in composition of long chain unsaturation fatty acids Membrane Rafts lipids and protein laterally organized forming microdomains of liquid order states o Protein rich in lipid aggregates that move in sea of phospholipids o High in sphingolipids and cholesterol o A number of transport and cell surface receptor proteins are associated with lipid raft o Many viruses associate w lipid raft and trigger import into cell o Folate receptor is found on lipid raft therefore fumonians toxins produced by fungi inhibit sphingosine synthesis These 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 Spinabifida outbreak in response to toxins Barriers and fences cause lateral diffusion restricted by membrane skeleton o Membrane floats on cytoskeleton proteins such as spectrin and actin Membrane skeleton o Must anchor scaffold to membrane o Used in erythrocyte o Facilitates anchoring of membrane to skeleton Spectrin 75 of skeleton composed of repeating segments that fold into 3 alpha helices hereditary defect of spectrin spherocytosis RBC rapid turnover Spectrin in RBC analogous to drystophan defect causing muscular dystrophy Ankyrin associates with spectrin and HCO3 Cl anion channel Membrane remodeling and curvature most change shape in response to events o Protein lipid curvature occurs via lipid imbalance conical protein shape helix insertion interacting with scaffold proteins cytoskeleton filaments Caveolae scaffolding proteins flask shaped invagination associated with integral membrane proteins named cavelins o As it dimerizes it pulls and forms flask o Participates in endocytosis and intracellular signaling Vesicle mediated transporto Proteins lipids and other materials are constantly reorganized and exchanged o Normal processes require membrane fusion or budding and separation Cell division exo endocytosis viral infection organelles communicate via trafficking vesicles o Transmembrane orientation is preserved meaning C and N terminus always conserved o Outside of cell is similar to inside of organelle o Vesicle fusion requires integral and lipid linked proteins SNARES R arg SNARES for vesicle and Q glu SNARE for the target Each helix has 7 pseudo residue repeats where and A and D are hydrophobicsimilar to keratin structure R and 3Q H bond serving to bring helices into proper orientation for fusion Lumen goes to outside of cell when fusion occurs and SNARES are recycled back o Tetanus and Botulism Toxin released by anaerobic bacteria Toxins are neurotoxins that inhibit the release of neurotransmitter Neurotoxins are 150KD polypeptides and are cleaved by host making a heavy and light chain Heavy chain facilitates L chain L chain cleaves target SNARE halting exocytosis of synaptic vesicle NEW UNIT Membrane transport o Transport across membranes diffusion from 1 side to next The difference in conc of substance on 2 sides generates chemical potential deltaG RTn Ad As movement of ions generates electric potential 2AFdeltapsi delta psi measures potential across membrane inside cell potential minus outside cell potential negative number indicates inside of cell more negative than outside o cytosol considered inside of cell