Biomembrane Structure & Function J a v a d F a s a J a m s h i d i U n i v e r s i t y o f M e d i c a l S c i e n c e s The Biomembrane The plasma membrane defines the cell and separates the inside from the outside. These biomembranes all have the same basic architecture-a phospholipid bilayer in which proteins are embedded They can bend and flex in three dimensions while still maintaining their integrity 2 Fluid Mosaic Model 3 The Bilayer Structure of Biomembranes 4 The Faces of Cellular Membranes 5 Image From: Lodish, Molecular Cell Biology 7e. 2013 The Faces of Cellular Membranes 6 Image From: Lodish, Molecular Cell Biology 7e. 2013 Three Classes of Biomembrane Lipids Differ in their chemical structures, abundance, and functions in the membrane Phosphoglycerides Sphingolipids Sterols 7 Phosphoglycerides 8 Phosphoglyceride Head Groups glycerol 3-phosphate 9 Sphingolipids All are derived from sphingosine, an amino alcohol with a long hydrocarbon chain, and contain a long-chain fatty acid attached in amide linkage to the sphingosine amino group In sphingomyelin, the most abundant sphingolipid, phosphocholine is attached to the terminal hydroxyl group of sphingosine 10 Sterols The major sterols in animals (cholesterol), fungi (ergosterol), and plants (stigmasterol) Like other membrane lipids, sterols are amphipathic. 11 Mobility of Lipids in Biomembranes 12 Phase Transition 13 Image From: Lodish, Molecular Cell Biology 7e. 2013 Lipid Composition is Different Between Membranes 14 Lipid Composition is Different Between Membranes 15 Lipid Composition in the Exoplasmic and Cytosolic leaflets A characteristic of all biomembranes is an asymmetry in lipid composition across the bilayer Unlike particular phospholipids, cholesterol is relatively evenly distributed in both leaflets of cellular membranes How the asymmetric distribution of phospholipids in membrane leaflets arises is still unclear. When cells die, lipid asymmetry is no longer maintained 16 lipid bilayer of human red blood cells Yellow= PhosphatidylEthanolamine Red= PhosphatidylCholine 17 Green= PhosphatidylSerine Brown= Sphingomyelin Lipid Rafts Because cholesterol and sphingomyelin are found in more ordered, less fluid bilayers, they can form microdomains, termed lipid rafts 18 Membrane Proteins Membrane proteins are defined by their location within or at the surface of a phospholipid bilayer Proteins associated with a particular membrane are responsible for its distinctive activities. The kinds and amounts of proteins associated with biomembranes vary depending on cell type and subcellular location. 19 Proteins Interaction with Membranes Membrane proteins can be classified into three categories on the basis of their position with respect to the membrane Integral Lipid-anchored Peripheral 20 Integral Membrane Proteins Transmembrane proteins, span a phospholipid bilayer and comprise three segments. The cytosolic and exoplasmic domains have hydrophilic exterior surfaces The membrane-spanning segments usually contain many hydrophobic amino acids The membrane-spanning domains consist of one or more α helices or of multiple β strands. 21 Integral Membrane Proteins (1) a single α helix (2) multiple α helices, (3) as a rolled-up β sheets(β barrel). 22 Lipid-anchored Membrane Proteins They are bound covalently to one or more lipid molecules. The hydrophobic segment of the attached lipid is embedded in one leaflet of the membrane and anchors the protein to the membrane. The polypeptide chain itself dose not enter the phospholipid bilayer. Examples include bacterial lipoproteins, G proteins and certain kinases 23 Lipid-anchored Membrane Proteins 24 Lipid-anchored Membrane Proteins 25 Peripheral Membrane Proteins Do not directly contact the hydrophobic core of the phospholipid bilayer Instead they are bound to the membrane either indirectly by interactions with integral or lipid-anchored membrane proteins or directly by interactions with lipid head groups Peripheral proteins can be bound to either the cytosolic or the exoplasmic face of the plasma membrane 26 Peripheral Membrane Proteins 27 Asymmetrically Orientation of Proteins Every type of transmembrane protein has a specific orientation, known as its topology, with respect to the membrane faces Transmembrane glycoproteins are always oriented so that all carbohydrate chains are in the exoplasmic Glycoproteins and glycolipids can interact with components of the extracellular matrix as well as lectins (proteins that bind specific sugars), growth factors, and antibodies. 28 ABO Blood Groups 29 Relative Permeability of a Pure Phospholipid Bilayer 30 Membrane Transport Proteins Movement of virtually all small molecules and ions across cell membranes is mediated by membrane transport proteins Each protein transports a particular class of molecule (such as ions, sugars, or amino acids) and often only certain molecular species of the class. Membrane transport proteins usually found to be multipass transmembrane proteins 31 Two Main Classes of Membrane Transport Proteins 32 Channels 33 Transporters 34 Types of Transport 35 Types of Transport 36