10 - Cell membranes Flashcards
main constituents of the lipid bilayer:
- phospholipids (sphingomyelin and phosphoglycerides)
- steroles (cholesterol)
- glycolipids (sphingolipids)
name three examples of phosphoglycerides and two examples of sphingomyelin
Phosphoglycerides:
phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine
sphingomyelins:
sphingomyelin and sphingosine
structure and function of phospholipids
polar head + nonpolar tail = amphiphilic
forms bilayers where the nonpolar parts are together and the polar heads are out toward the polar environment
the polar heads confer specificity for interactions with membrane proteins
the length and amount of cis-bonds in the lipid tails affect fluidity of the membrane. Cis double bonds create kinks which affect packing/fluidity of the membrane. more cis = more fluid, less kinks = straight and tightly packed.
sterols structure and functions
polar -OH group, followed by a rigid ring structure and a short non-polar tail
cholesterol affects membrane permeability
movement within the membrane
the lipid bilayer allows lateral () movement of the lipids. they also sometimes flip-flop to get to the other layer, but it is more rare. Diffusion rate is correlated with membrane composition
and temperature changes. It has to be tightly controlled
to permit specific
flippases (or phospholipid translocators) help them move from one monolayer to the other - essential because they are usually synthetized in one (cytosolic of ER membrane), but are needed elsewhere maybe
What determines the fluidity of the membrane?
structure/composition and temperature.
Phase-transition is when the phospholipid bilayer changes from a fluid state to a gel-like state.
temperature affects the phase-transition (warmer = fluid, colder = gel)
Fatty acid chain lenght: Short- lower phase transition temperature, Long- higher phase transition temperature
cis-double bonds: Lower phase transition temperature
cholesterol: increased stiffness, reduced permeability
Yeast and bacteria, whose temperature fluctuations with the environmental
compensate by adjusting the fatty aci
glycolipids structure and function
Glycolipids are lipids containing sugar molecules, they are responsible for the most extreme asymmetry in their membrane distribution. They are always on the non-cytosolic monolayer. In animal cells they are made from sphingosine, like sphingomyelin
Hints to the function of glycolipids come from their localization. In epithelial cells, glycolipids are confined to the exposed apical surface, where they may help to protect the membrane against the ahrsh conditions frequently found there (low pH, higg [degradative enzymes]). Charged glycolipids may be improtant because of their electrical effects, their presence alters the electrical field across the membrane and the concentration of ions - esp Ca2+ - at the membrane surface. Glycolipids also function in cell-rec processes in which membrane-bound CH (carbohydrate(-binding proteins (lectins) bind to the sugar groups on both glycolipids and glycoproteins in the procoess of cell-cell adhesion. Mutant mice that are deficient in all of their complex gangliosides show abnormalities in the nervous system, including axonal degeneration and reduced muelination.
Some glycolipids provide entry points for certain bacterial toxins and viruses. The ganglioside G_M1 acts as a cell-surface receptor for bacterial toxin that causes the delibitating diarrhea of cholera.
asymmetry of the bilayer
Assymetry is maintained by phospholipid translocators (flippases)
Phospholipid molecules in the outer membrane contain mostly phosphatidylcholine and sphingomyelin; whereas in the inner membrane mostly phosphatidylserine and phosphatidylethanolamine
Importance:
Lipid asymmetry is important, esp for converting extracellular signal into intracellular signals.
Gycolipids only on extracellular part of plasma membrane - important for cell recognition and -communication, protection (apical surface of stomach epithelium, plant and animal immunity), can also be receptors for bacterial toxins and are also important in myelin sheath (used for electrical insulation of nerves)
Also for distinguishing between live and dead cells. When animal cells undergo apoptosis, phosphatidylserine (normally confined to cytosolic monolayer) rapidly translocates to the extracellular monolayer. It is exposed on the cell surface, signaling neighboring cells like macrophages to phagocytose it. The translocation og the phosphatidylserine in apoptotic cells is thought to occur by two mechanisms:
1. The phospholipid translocator that normally transports this lipid from the outer to the inner monolayer is inactivated 2. A "scramblase" that transfers phospholipids nonspecifically in both directions between the two monolayers is activated.
How are extracellular signals converted into intracellular signals?
Many examples.
Many cytosolic proteins bind to specific lipid head groups in the cytosolic membrane layer. The enzyme protein kinase C (PKC) is an example, it is activated in response to various extracellular signals, binds to the cytosolic face og the plasma membrane, and requires this negatively charged phospholipid (phosphatidylcholine) for its activity.
In other cases, specific lipid head groups must first be modified to create protein-binding sites at a particular time and place. One example is phosphatidylinositol (PI), one of the minor phospholipids that are concentrated in the cytosolic monolayer. Various lipid kinases can add phosphate groups at distinct positions on the inositol ring, creating binding sites that recruit specific proteins from the cytosol to the membrane. An important example is PI 3 kinase, which is activated in response to extracellular signals and helps to recruit specific intracellular signaling proteins to the cytosolic face of the membrane. Similar lipid kinases phosphorylate inositol phospholipids in intracellular membranes, and thereby help to recruit proteins that guide membrane transport.
Phospholipids in the plasma membrane are used in yet another way to convert extracellular signals. The plasma membrane contains various phospholipases, which are activated by extracellular signals to cleave specific phospholipid molecules, generating fragments of these molecules that act as short-lived intracellular mediators. Phospholipase C cleaves an inositol phospholipid in the cytosolic monolayer of the membrane to generate two fragments, one of which remains in the membrane and helps activate PKC, while the other us released into the cytosol to stimulate the release of Ca2+ from the ER.
Production and storage of membrane lipids
biosynthesis in ER; stored in lipid droplets, unique organelles surrounded by a single monolayer of lipids. fatty acids can be liberated from lipid droplets on demand and transported to other places in the body.
Association of membrane proteins with the lipid bilayer-overview
Integral membrane proteins are often amphiphilic (hydrophilic and hydrophobic domains)
Multiple ways they can be attached:
Most membrane proteins are thought to extend across the bilayer as:
1. A single α helix
2. Multiple α helices
3. A β-barrel
Some of these single-pass or multi-pass proteins have a covalently attached fatty acid chain inserted in the cytosolic lipid monolayer (1). Other membrane proteins are exposed at only one side of the membrane. (4) some of these are anchored to the cytosolic surface by an amphiphilic α helix that partitions into the cytosolic monolayer through the hydrophobic face of the helix. (5) others are attached to the bilayer solely by a covalently bound lipid chain - either fatty acid or prenyl group) - in the cytosolic monolayer, or (6) via an oligosaccharide linker, to phosphatidylinositiol in the noncytosolic monolayer - called the GPI anchor. (7,8) Finally, membrane-associated proteins are attached to the membrane only by noncovalent interactions with other membrane proteins.
transmembrane proteins
In most TM proteins the polypeptide chain crosses the bilayer in an α-helical configuration
Peptide bonds are polar- need to form hydrogen bonds in the absence of water- hydrogen bonding is maximised in the α-helical configuration
Membrane spanning segments of the polypeptide chain contact
hydrophobic environment of lipid bilayer and are largely amino
acids with non-polar side chains (hydrophobic amino acids)
• Interaction between α-helices occurs in both single and multi-pass TM proteins • Crucial for the structure and function of many channels and transporters which move molecules across membranes
TM proteins can contain both fully and partially membrane crossing αhelices.
Eg. Aquaporin: tetrameric formation (a monomer shown here) produces a channel that allows water to enter the cells.
Outside: hydrophobic; inside: hydrophilic
How the protein is attached to the membrane will affect the function. Transmembrane proteins can have functions on both sides, or transport molecules across it. Cell-surface receptors cannot do that. Proteins that function on only one side are typically associated exclusively with either the lipid monolayer or a protein domain on that side
transmembrane proteins containing β-sheets can form β-barrels of varying diameters
Porins
Form channels for transport of ions and small molecules
Pore diameter can determine exclusion limit
Fairly rigid structure: H-bonds bind the sheets rigidly to each other
E.g. TM proteins located in outer membranes of mitochondria, chloroplasts and bacteria.
• - Can function as receptors (1 E coli OmpA receptor for bacteriophages) or lipases (2 E coli OMPLA protein-no
pore).
• - Can allow passage of polar molecules through the inside (3 16-stranded porin).
• - molecular selectivity can be conferred via the extracellular loops (4 FepA protein capable of iron transport
membrane glycoproteins
Many transmembrane/membrane proteins are glycosylated
Glycoproteins: mono- oligo- or poly- saccharides covalently bound to
membrane proteins
• Proteoglycans: protein glycosylated by 1 or more glycosaminoglycans
(GAGs)- often long chains e.g. heparin and hyaluronic acid
functions of the glycolax
Protection against mechanical and chemical damage (mucus membranes) • Pathogen recognition/invasion • Cell recognition (self vs non-self) • Signalling- activate receptors on the surface of cells
