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The Structure of Biological Membranes
Func7ons of Cellular Membranes 1. Plasma membrane acts as a selec7vely permeable barrier to the
environment
• Uptake of nutrients
• Waste disposal • Maintains intracellular ionic milieau
2. Plasma membrane facilitates communica7on • With the environment
• With other cells • Protein secre8on
3. Intracellular membranes allow compartmentaliza7on and separa7on of different chemical reac7on pathways
• Increased efficiency through proximity
• Prevent fu8le cycling through separa8on
Composi7on 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 proper8es
• 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 FaJy Acid
• Palmitate and stearate most common • 14-‐26 carbons • Even # of carbons
Unsaturated FaJy 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
Phospha8dylethanolamine
Phospha8dylcholine
Phospha8dylserine
Phospha8dylinositol Ether Bond at C1
PS and PI bear a net nega8ve charge at neutral pH
Sphingolipids are the Second Major Class of Phospholipid in Animal Cells
Sphingosine
Ceramides contain sugar moi8es 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 associa7on 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 Forma7on is Driven by the Hydrophobic Effect
• HE causes hydrophobic surfaces such as faVy 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 (ΔG) of the system by maximizing the entropy (ΔS) or degree of disorder of the water molecules
• ΔG = ΔΗ ‒ ΤΔS
Figure 1-12 Molecular Biology of the Cell, Fifth Edition (© Garland Science 2008)
Lipid Bilayer Forma7on is a Spontaneous Process
Gently mix PL and water
Vigorous mixing
Figure 10-8 Molecular Biology of the Cell (© Garland Science 2008)
The Forma7on of Cell-‐Like Spherical Water-‐Filled Bilayers is Energe7cally 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 Transi7on
Below Lipid Phase Transi7on Temp Above Lipid Phase Transi7on Temp
Gauche Isomer Forma7on
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 Composi7ons
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 Selec7vely 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 Transduc7on
PI-‐4,5P PI-‐3,4,5P
1. Ac7va7on of Lipid Kinases
2. Phospholipases Produce Signaling Molecules via the Degrada7on of
Phospholipids
Figure 10-17b Molecular Biology of the Cell (© Garland Science 2008)
Phospholipase C Ac7va7on 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-‐Limi8ng Step in ER)
Figure 10-14b Molecular Biology of the Cell (© Garland Science 2008)
Lipid Rads 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 Visualiza7on of Lipid Rads in Ar7fical Bilayers
Yellow spikes are GPI-‐anchored protein
3 Ways in which Lipids May be Transferred Between Different Intracellular Compartments
Vesicle Fusion Direct Protein-‐Mediated
Transfer Soluble 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 Mul7-‐pass
FaJy acyl anchor
GPI Anchor
Transmembrane Helix
Linker Domain
β-‐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)
Func7onal Characteriza7on of Integral Membrane Proteins Requires Solubiliza7on and Subsequent Recons7tu7on into a Lipid Bilayer
(Used to denature proteins)
(Used to purify Integral Membrane Proteins)
Detergents are Cri7cal 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 Solu7on
(Cri8cal Micelle Concentra8on)
Detergent Solubiliza7on of Membrane Proteins
Desirable for Purifica8on of Integral Membrane Proteins
Beta Sheet Secondary Structure
An7-‐parallel Strands
Side chains alternately extend into opposite sides of the sheet
H-‐Bond
Polypep7de backbone is maximally extended (rise of 3.3 Å/residue)
β-‐Barrel Structure of the OmpX Porin Protein in the Outer Membrane of E. coli
Aroma7c Side Chain anchors
Alterna7ng Alipha7c Side Chains
Transmembrane α-‐Helices 1. Right-‐handed 2. Stability in bilayer results from
maximum hydrogen bonding of pep8de backbone
3. Usually > 20 residues in length (rise of 1.5 Å/residue)
4. Exhibit various degrees of 8lt with respect to the membrane and can bend due to helix breaking residues
5. Mostly hydrophobic side-‐chains in single-‐pass proteins
6. Mul8-‐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 Oden be Accurately Iden7fied 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 Waals Contact
Figure 10-34 Molecular Biology of the Cell (© Garland Science 2008)
Structure of the Photosynthe7c Reac7on 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 Interac8ons
Interac8on with the cytoskeleton
Interac8on with the extracellular maxtrix
Intercellular Protein-‐Protein Interac8ons
