Membranes Lecture PDF

Membranes BIOL2020 Prof. Nicanor González Proteins are made here Not here The fluid mosaic model envisions the membrane as a fluid bilayer of lipids with a mosaic of associated proteins Membranes contain several classes of lipids membranes vary in lipid composition The lipid bilayer is flu...

Membranes BIOL2020 Prof. Nicanor González Proteins are made here Not here The fluid mosaic model envisions the membrane as a fluid bilayer of lipids with a mosaic of associated proteins Membranes contain several classes of lipids membranes vary in lipid composition The lipid bilayer is fluid and asymmetric ● Phospholipids diffuse Translocases are proteins that move phospholipids between layers and maintain the lipid asymmetry membrane translocases Fan J., Wang X., Sun Z., Zhou X. (2018) Membrane Asymmetry and Phospholipid Translocases in Eukaryotic Cells. FRAP (Fluorescence recovery after photobleaching) a method to study the mobility of molecules in living cells FRAP was used to test the movement of membrane proteins Proteins at the membrane must have hydrophobic amino acids ● Stretch of hydrophobic amino acids are the hydrophobic region of membrane proteins Membranes contain integral, peripheral, and lipid-anchored proteins • Integral have a hydrophobic region • Peripheral proteins associate though another membrane protein • Lipid-anchored proteins bind fatty acids which gets inserted into the membrane Membrane proteins detect and transmit electrical and chemical signals Insulin Insulin Receptor Chemical signals bind to membrane receptors Insulin receptor, with the extracellular portion at the top, intracellular portion at the bottom, and the cell membrane shown schematically in gray. https://pdb101.rcsb.org/motm/182 Membrane proteins mediate cell adhesion and cell-cell communication ● cadherin to cadherin binding keep cells together Transmembrane proteins can also move ions across cell membranes. The calcium pump goes through a cycle of changes in the process of pumping Conformational changes in the pumping cycle: empty state (left) and with calcium bound (right). Most Integral proteins are transmembrane Proteins (Cross the membrane) GLUT3 is shown on the left in the open outward conformation, and GLUT1 is shown on the right in an open inward conformation. Acetylcholine receptor, with the binding site for acetylcholine in red. The membrane is shown schematically in gray. Integral Monotopic Proteins are only on one side of the membrane 1. 2. 3. 100% embed into a single face of the membrane. Irreversible reactions involving hydrophobic or amphiphilic substrates not readily soluble in water. 0% 1. 2. COX-2/Prostaglandin H2 synthase (COX-2/PGHS) Glycerol-3-phosphate dehydrogenase (GlpD) Peripheral membrane proteins form weak and reversible associations to the membrane, typically through binding to integral membrane proteins digest lipids Examples ● ● Enzymes that metabolize membrane lipids Regulatory subunits of transmembrane proteins Phospholipase A2 breaks membrane lipids. Pancreatic and cytosolic phospholipase A2. A membrane is shown schematically in gray. signaling Lipid-anchored membrane proteins are covalently bound to fatty acids or isoprenyl groups Glycosylphosphatidylinositol Isoprenyl post-translational modification that resulted in attachment of hydrophobic prenyl groups that anchor the small GTPAse proteins to intracellular membranes Ras protein with a non-hydrolyzable analogue of GTP. Trehalase is an example of a lipid-anchored membrane protein glucose Trehalose Trehalase glucose Trehalase is bound to Glycosylphosphatidylinositol Proteins and lipids in the outside of the membrane are glycosylated asparagine (Asn) serine (Ser) or threonine (Thr) Glycosylation is the process by which a carbohydrate is covalently attached to a target macromolecule N-linked glycosylation of asparagine O-linked glycosylation of serine or threonine Summary Fluid mosaic ● Lipids and proteins ● Both move Protein association with membrane ● Integral ○ Transmembrane ○ Monotopic ● Peripheral ● Lipid-anchored Lipid composition ● Different between membranes ● Different between layers Post-translational modifications ● Attachment of lipophilic groups ○ GPI ○ Isoprenylation ● Glycosylation ○ Outside