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Chapter 11: Biological Membranes and Transport
Dr. Clower
Chem 4202
Lipid Aggregates
Lipids are not “free”
Virtually insoluble in water
Associate to form separate phase
– Reduces contact of nonpolar chain with H2O
– Solvate polar head groups
Micelles
Bilayers– Structural basis for biological membranes
Micelles Spherical 10 – 1000s of lipids Free fatty acids Detergents
Bilayer
Two monolayers (leaflets) 3 nm (30 Å) thick Lipids are structurally similar
– Glycerophospholipids
– Sphingolipids
Liposome
Bilayer folded back on itself Hollow sphere Maximum stability in aqueous environment
– Loss of hydrophobic edge of bilayer
Biological Membranes
Surround cells Partition two aqueous environments of different
concentrations Formed from lipid bilayers
– Inner and outer leaflet
Flexible– Change shape without compromising integrity
Lipid mobility– Transfer of lipid through bilayer
Transverse diffusion Lateral diffusion
Transverse Diffusion
“Flip-flop” From one bilayer
leaflet to the other Rare Very slow without
catalyst– Polar head pass
through anhydrous core
– Catalyst = flippase
Lateral Diffusion Exchange of neighboring lipids in same bilayer
leaflet
Measure with: – Fluorescence recovery after photobleaching (FRAP)– Single particle tracking
FRAP
Single Particle Tracking
Membrane Fluidity Changes in conformation of chains
keep interior in constant motion– Low viscosity in interior– Increases close to head (limited
mobility) Liquid-disordered state (fluid)
vs. liquid-ordered statevs. paracrystalline state (gel)
Temperature dependent Favored by unsaturated FAs,
shorter FAs Sterols
– Reduce fluidity– Reduce freedom of movement/rotation
Membrane Fluidity
Lipids synthesized by cells to keep fluidity constant
Membrane Structure and Assembly Contain lipids and proteins
– Percent composition varies with function
Lipids – Can be the same or different– Most commonly:
Glycerophospholipids, sphingolipids, and sterols
Membrane Proteins Composition varies
– More widely than lipids Catalyze chemical
reactions Relay information Transport across
membranes 3 classes
A. Integral/intrinsicB. Lipid-linkedC. Peripheral/
extrinsic
A. Integral Proteins
Strongly associate to membranes– Hydrophobic interactions
Difficult to separate from membrane– Need detergent, denaturant
Amphiphilic– Nonpolar section in membrane– Polar section(s) on one or both sides of
membrane Example: cyclooxygenase
COX-1 with NSAID
Intergral Membrane Proteins Types I - VI Transmembrane
proteins– Span membrane– 3 domains– Preference for one
face or the other– Sugar residues
outside
Transmembrane Domain
Hydrophobic region Domain structure
– a-helix– b-barrel
Protein tertiary structure difficult to determine– 10-20% are integral– 1% structure determined
Predict presence when > 20 nonpolar AA residues
Use hydropathy index
Hydropathy Index
Free energy change accompanying movement of AA side chain from hydrophobic solvent into water– Charged or polar =
exergonic– Aromatic, aliphatic =
endergonic
Glycophorin ASingle a-helix
Bacteriorhodopsin7 helices connected by hydrophilic loops
Threonine and Tyrosine Interact with both polar and nonpolar regions Located on surface
Tyr = orange Thr = red Charged = blue
Rhodopseudomonas viridis Photosynthetic
reaction center 1200 residues 1st protein determined
by crystallography 4 non-identical
subunits Transmembrane
section = 11 a-helices Red = prosthetic
groups
b-barrel b-sheets not found in membrane interior b-barrels are 16-20 stranded anti-parallel sheet Typically 7-9 residues to span Alternate residues (at least) are hydrophobic
– Interact with lipid Ex: porins
– Found in membranes of gram-negative bacteria– Trimers of identical subunits – Barrel forms channel
Allows entry of charged/polar molecules R groups in channel can be polar
Membrane Proteins with b-Barrel Structure
B. Lipid-linked proteins
Covalently attached to lipids (anchor) Not as strongly associated as integral;
more strongly associated than peripheral 3 varieties
1. Prenylated proteins
2. Fatty acylated proteins
3. GPI-linked proteins
1. Prenylated proteins Lipid synthesized
from isoprene Linkage to Cys
residue at C-terminus
2. Fatty Acylated Proteins Myristic acid (14:0)
– Links to amine N of Gly at N-terminus
Palmitic acid (16:0)– Thioester linkage to
internal Cys
3. GPI-linked Proteins Glycosyl-
phosphatidylinositol Exterior surface only Glycerophospholipid
linked to tetrasaccharide – (3 Man; 1 Glc) – linked to C-terminus
through ethanolamine phosphate
C. Peripheral/Extrinsic Proteins
Easy to separate from membranes
Associate with membranes by binding at surface to lipids or integral proteins– H-bond or electrostatic
Do not bind lipids Regulate membrane-
bound enzymes or limit mobility of integral proteins (tether to intracellular structures)
Assembly of Membranes Fluid-mosaic model Proteins move in membranes due to lipid mobility Leaflets not equivalent in composition or function
Transport across Membranes
Nonmediated– Diffusion of nonpolar
molecule through membrane– From high concentration to
low concentration
Mediated– Through action of specific
proteins– Carrier proteins– Integral protein channels
Carrier Proteins Shuttle amino acids, ions, sugars etc. into cells Hydrophobic on outside Specific for ligands/substrates
Integral Protein Channels Means by which hydrophilic molecules/ions move
through hydrophobic membrane Typically selective for one molecule/ion Channel = protein complex
– Transverse cell membrane– Hollow, hydrophilic core– Hydrophobic outside interact with lipids
Transport Systems Integral proteins with binding sites on
either side of membrane Reversible process More than one type of molecule can be
transported Ex: lactose transporter of E. coli
– Lactose and H+
Summary of Transport Types
Chapter 11 Problems
3-4, 6, 11-15, 18