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Functions of Cellular Membranes1. Plasma membrane acts as a selectively permeable barrier to the
environment• Uptake of nutrients• Waste disposal• Maintains intracellular ionic milieu2. Plasma membrane facilitates communication• With the environment• With other cells3. Intracellular membranes allow compartmentalization and separation of different chemical reaction pathways• Increased efficiency through proximity• Prevent futile cycling through separation
• Protein secretion
Composition of Animal Cell Membranes
• Hydrated, proteinaceous lipid bilayers• By weight: 20% water, 80% solids• Solids: Lipid Protein Carbohydrate (~10%)• Phospholipids responsible for basic membrane bilayer
structure and physical properties• Membranes are 2-dimensional fluids into which
proteins are dissolved or embedded
~90%
The Most Common Class of Phospholipid is Formed from a Gycerol-3-P Backbone
Saturated Fatty Acid
•Palmitate and stearate most common•14-26 carbons•Even # of carbons
Unsaturated Fatty Acid
Figure 10-2 Molecular Biology of the Cell (© Garland Science 2008)
Structure of Phosphoglycerides
All Membrane Lipids are Amphipathic
Phosphoglycerides are Classified by their Head Groups
Phosphatidylethanolamine
Phosphatidylcholine
Phosphatidylserine
PhosphatidylinositolEther Bond at C1
PS and PI bear a net negative chargeat neutral pH
Sphingolipids are the Second Major Class of Phospholipid in Animal Cells
Sphingosine
Ceramides contain sugar moities in ether linkage to sphingosine
Figure 10-18 Molecular Biology of the Cell (© Garland Science 2008)
Glycolipids are Abundant in Brain Cells
Membranes are formed by the tail to tail association of two lipid leaflets
Cytoplasmic Leaflet
Exoplasmic Leaflet
Figure 10-11a Molecular Biology of the Cell (© Garland Science 2008)
(Hydrophobic)
(Hydrophilic)
Bilayers are Thermodynamically Stable Structures Formed from Amphathic Lipids
Lipid Bilayer Formation is Driven by the Hydrophobic Effect
• HE causes hydrophobic surfaces such as fatty acyl chains to aggregate in water
• Water molecules squeeze hydrophobic molecules into as compact a surface area as possible in order to the minimize the free energy state (G) of the system by maximizing the entropy (S) or degree of disorder of the water molecules
• DG = – DH TDS
Figure 1-12 Molecular Biology of the Cell, Fifth Edition (© Garland Science 2008)
Lipid Bilayer Formation is a Spontaneous Process
Gently mix PL and water
Vigorous mixing
Figure 10-8 Molecular Biology of the Cell (© Garland Science 2008)
The Formation of Cell-Like Spherical Water-Filled Bilayers is Energetically Favorable
Figure 10-7 Molecular Biology of the Cell (© Garland Science 2008)
Phospholipids are Mesomorphic
Figure 10-11b Molecular Biology of the Cell (© Garland Science 2008)
PhosphoLipid Movements within Bilayers(µM/sec)
(1012-1013/sec) (108-109/sec)
Pure Phospholipid Bilayers Undergo Phase Transition
Below Lipid Phase Transition Temp Above Lipid Phase Transition Temp
Gauche Isomer Formation
All-Trans
Figure 12-57 Molecular Biology of the Cell (© Garland Science 2008)
Phosphoglyceride Biosynthesis Occurs at the Cytoplasmic Face of the ER
Figure 12-58 Molecular Biology of the Cell (© Garland Science 2008)
A “Scramblase” Enzyme Catalyzes Symmetric
Growth of Both Leaflets in the ER
Figure 10-16 Molecular Biology of the Cell (© Garland Science 2008)
The Two Plasma Membrane Leaflets Possess Different Lipid Compositions
Enriched in PC, SM, Glycolipids
Enriched in PE, PS, PI
Figure 12-58 Molecular Biology of the Cell (© Garland Science 2008)
A “Flippase” Enzyme promotes Lipid
Asymmetry in the Plasma Membrane
Membrane Proteins May Selectively Interact with Specific Lipids (Lipid Annulus or Halo)
Lipid Asymmetry Also Exists in the Plane of the Bilayer
Figure 10-17a Molecular Biology of the Cell (© Garland Science 2008)
Phospholipids are Involved in Signal Transduction
PI-4,5P PI-3,4,5P
1. Activation of Lipid Kinases
2. Phospholipases Produce Signaling Molecules via the Degradation of
Phospholipids
Figure 10-17b Molecular Biology of the Cell (© Garland Science 2008)
Phospholipase C Activation Produces Two Intracellular Signaling Molecules
PI-3,4,5P
I-3,4,5P
Diacylglycerol
Hydrophilic End
Flexible Hydrocarbon Tail
Amphipathic Lipids Containing Rigid Planar Rings Are Important Components of Biological Membranes
Figure 10-5 Molecular Biology of the Cell (© Garland Science 2008)
C12
How Cholesterol Integrates into a Phospholipid Bilayer
Cholesterol Biosynthesis Occurs in the Cytosol and at the ER Membrane Through Isoprenoid Intermediates
(Rate-Limiting Step in ER)
Figure 10-14b Molecular Biology of the Cell (© Garland Science 2008)
Lipid Rafts are Microdomains Enriched in Cholesterol and SM that may be Involved in Cell
Signaling Processes
Insoluble in Triton X-100
Figure 10-14a Molecular Biology of the Cell (© Garland Science 2008)
Electron Force Microscopic Visualization of Lipid Rafts in Artificial Bilayers
Yellow spikes are GPI-anchored protein
3 Ways in which Lipids May be Transferred Between Different Intracellular Compartments
Vesicle FusionDirect Protein-Mediated
TransferSoluble Lipid
Binding Proteins
Figure 10-19 Molecular Biology of the Cell (© Garland Science 2008)
The 3 Basic Categories of Membrane Protein
Integral Lipid-Anchored
Peripheral(can also interact via PL headgroups)
Single-Pass Multi-pass
Fatty acyl anchor
GPI Anchor
Transmembrane Helix
Linker Domain
b-Strands
Figure 10-20 Molecular Biology of the Cell (© Garland Science 2008)
3 Types of Lipid Anchors
Figure 3-5 Molecular Biology of the Cell (© Garland Science 2008)
Membrane Domains are “Inside-Out”
Right-Side Out Soluble Protein
Figure 10-31 Molecular Biology of the Cell (© Garland Science 2008)
Functional Characterization of Integral Membrane Proteins Requires Solubilization and Subsequent Reconstitution into a Lipid Bilayer
(Used to denature proteins)
(Used to purify Integral Membrane Proteins)
Detergents are Critical for the Study of Integral Membrane Proteins
Figure 10-29b Molecular Biology of the Cell (© Garland Science 2008)
Detergents Exist in Two Different States in Solution
(Critical Micelle Concentration)
Detergent Solubilization of Membrane Proteins
Desirable for Purification of Integral Membrane Proteins
Beta Sheet Secondary Structure
Anti-parallel Strands
Side chains alternately extend into opposite sides of the sheet
H-Bond
Polypeptide backbone is maximally extended (rise of 3.3 Å/residue)
b-Barrel Structure of the OmpX Porin Protein in the Outer Membrane of E. coli
Aromatic Side Chain anchors
Alternating Aliphatic Side Chains
Transmembrane a-Helices1. Right-handed2. Stability in bilayer results from
maximum hydrogen bonding of peptide backbone
3. Usually > 20 residues in length (rise of 1.5 Å/residue)
4. Exhibit various degrees of tilt with respect to the membrane and can bend due to helix breaking residues
5. Mostly hydrophobic side-chains in single-pass proteins
6. Multi-pass proteins can possess hydrophobic, polar, or amphipathic transmembrane helices
H-Bond
Figure 10-22b Molecular Biology of the Cell (© Garland Science 2008)
Transmembrane Domains Can Often be Accurately Identified by Hydrophobicity Analysis
Figure 10-32 Molecular Biology of the Cell (© Garland Science 2008)
Bacteriorhodopsin of Halobacterium
Figure 10-33 Molecular Biology of the Cell (© Garland Science 2008)
Structure of Bacteriorhodopsin
Structure of the Glycophorin A Homodimer
Arg and Lys Side Chain Anchors
23 residue transmembrane helices
Coiled-Coil Domains in Van Der WaalsContact
Figure 10-34 Molecular Biology of the Cell (© Garland Science 2008)
Structure of the Photosynthetic Reaction Center of Rhodopseudomonas Viridis
Figure 10-39 Molecular Biology of the Cell (© Garland Science 2008)
4 Ways that Protein Mobility is Restricted in Biological Membranes
Intramembrane Protein-Protein Interactions
Interaction with the cytoskeleton
Interaction with the extracellular maxtrix
Intercellular Protein-Protein Interactions
