IBBT622D: Special Topics in Membrane Biology Cell Membranes, Membrane Proteins, Membrane-­‐Mediated Biological Processes, & Membrane Biotechnology Lecture 1.1. Tales of Two Molecules: Membrane Lipids & Membrane Proteins Cells are Rich in Membranes EM images of plasma cells
High S/V ratio
Assuming the cell is a sphere of 10 µm radius
Total [lipid] in PM ≈
Total [lipid] ≈
Protein crowding
Membranes in eukaryoIc cells. Cell membranes: Early Models Cell membranes: Fluid Mosaic Model Singer & Nicholson (1972) Science 175:720-731
•  The lipid bilayer as a permeability barrier and host for membrane
proteins
•  Membrane proteins: free
homogeneity), but no
(Brownian, lateral
Cell membranes: Present Models Engelman, Nature (2005), 438, 578; Kusumi et al., Ann Rev. Biophys. Biomol. Struct (2005), 34, 351
Jacobson et al, Nature Cell Biol (2007), 9, 7
Updated version: lipid-protein composite
i) Membrane proteins:
ii) Thickness:
iii) Transbilayer
iv) Lateral
v) Curvature:
P/L =
(w/w) for erythrocyte plasma membrane
for mitochondria
for myelin
Heterogeneity in cell membranes Curvatures in cell membranes McMahon & Gallop, Nature (2005), 438, 590
Tales of Two Molecules: Membrane Proteins & Lipids Membrane Proteins
1)
% x 25,000
2)
% of current drug targets (GPCRs & channels)
3) Diverse functions: receptors, channels, transporters, & etc
4) An active area of structural biology
What about lipids?
“Nucleic acids and proteins are informational macromolecules…On the other hand, polysaccharides
and lipids do not have information-carrying function” Lehninger, A. L. Biochemistry: the molecular basis of
cell structure and function (1975).
1) Serve as permeability barriers and provide
(
)
2) Solubilize
3) Then, why there are so many lipids?
4)
5)
Lecture 1.2. Structures & ProperIes of Membrane Lipids Major Lipids of Cell Membranes Glycerophospholipids
Sphingophospholipids
sn-1
sn-2
SAPC
Sterols
SM
Glyco(sphingo)lipids
Cholesterol
GM1 ganglioside
Lipid Headgroup & Hydrophobic Tails in the Bilayer 30Å Hydrocarbon region (core) O
OO
O
O
P
O O
O
O
NH3
+
OO
O
O
P
O O
15Å Interfacial region O
NH3
+
15Å (Glycero)Phospholipid Structures: Headgroup Two neutral PLs: PC vs. PE PC
PE
O
O
O
O
O
O
OO
O
P O
O
O
O
P
O
O
O
N
+
+
NH3
(Glycero)Phospholipid Structures: Acyl chains Saturated vs. Unsaturated FA ω-­‐3 vs. ω-­‐6 PUFA Docosahexaenoic acid (DHA) arachidonic acid (AA) Eicosapentaenoic acid (EPA) 1-­‐Stearoyl-­‐2-­‐docosahexaenoyl-­‐sn-­‐glycero-­‐3-­‐phospho-­‐
L-­‐serine (SDPS) (Brain) 1-­‐Stearoyl-­‐2-­‐arachidonoyl-­‐sn-­‐glycero-­‐3-­‐ [phosphoinositol-­‐4,5-­‐bisphosphate] (PIP2) Structure of sphingolipids Sphingomyelin SOPC Structures of sterols cholesterols
Cholesterol esters
Oxyterols
Phase TransiIon of Lipids Lβ Pβ
Lα or Ld Lipids FA composiIon Tm (oC) PalmiJc acid 16:0 63.1 Oleic acid 18:1 13.4 Arachidonic acid 20:4 -­‐49.5 POPC 16:0 18:1 -­‐2 DMPC 14:0 23 DPPC 16:0 41 Effect of Cholesterol on Membrane Structure SL-Chol & SL-SL Association: Lipid Rafts?
PC
SM
Cholesterol
Polymorphic phases of phospholipids: Polymorphism The molecular shape hypothesis of amphiphiles Molecular
Shape
O
O
OO
O
O
OO
O
O
P O
O
O
O
O
P O
O
N
+
PC
Cylinder
+
NH3
PE
Cone
O
OH
O
O
P
O
O
N
+
LysoPC
Inverted Cone
Physical
States
Micelles bilayer Lamellar Inverted (reverse) micelles HII HI Membrane Curvature
Molecular
Shape
O
O
O
O
OO
O
O
P O
O
O
O
O
P O
O
Curvature
OO
N
+
+
NH3
O
OH
O
O
P
O
O
N
+
Differential Effects of Lipids on Membrane Curvature
Membrane Curvature & Membrane Remodeling
Fusion
Fission