Molecular Biochemistry I

Lipids and Membrane Structure


Textbook Reading: Voet & Voet, Biochemistry, 3rd Edition, Chapter 12, sections 1-3. (Membrane assembly, protein targeting, and plasma lipoproteins will not be covered here.)

Some recent articles (optional reading): 
J. A. Killian & G. von Heijne (2000) "How proteins adapt to a membrane-water interface," Trends in Biochem. Sci. 25: 429-434.
R. M. Garavito & S. Ferguson-Miller (2001) "Detergents as tools in membrane biochemistry," J. Biol. Chem. 276: 32403-32406.
M. Edidin (2003) "The state of lipid rafts: from model membranes to cells," Annu. Rev. Biophys. Biomol. Struct. 32: 257-283.
M.-J. Bijlmakers & M. Marsh (2003) "The on-off story of protein palmitoylation," Trends in Cell Biol. 13: 32-42.
H. M. McConnell & M. Vrljic (2003) "Liquid-liquid immiscibility in membranes," Annu. Rev. Biophys. Biomol. Struct. 32: 469-492.
P. F. Devaux & R. Morris (2004) "Transmembrane asymmetry and lateral domains in biological membranes," Traffic 5: 241-246.
S. Degroote, J. Wolthoorn & G. van Meer (2004) "The cell biology of glycosphingolipids," Seminars in Cell & Develop. Biol. 15: 375-387.
S. Mukherjee & F. R. Maxfield (2004) "Membrane domains," Annu. Rev. Cell Dev. Biol. 20: 839-866.
T. Balla (2005) "Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions," J. Cell Sci. 118: 2093-2104.
L. Rajendran & K. Simons (2005) "Lipid rafts and membrane dynamics," J. Cell Sci. 118: 1099-1102.
A. Kusumi, C. Nakada, K. Ritchie, K. Murase, K. Suzuki, H. Murakoshi, R. S. Kasai, J. Kondo & T. Fujiwara (2005) "Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: High-speed single-molecule tracking of membrane molecules," Annu. Rev. Biophys. Biomol. Struct. 34: 351-378.
R. G. Parton, M. Hanzal-Bayer & J. F. Hancock (2006) "Biogenesis of caveolae: a structural model for caveolin-induced domain formation," J. Cell Sci. 119: 787-796.
T. J. McIntosh & S. A. Simon (2006) "Roles of bilayer material properties in function and distribution of membrane proteins," Annu. Rev. Biophys. Biomol. Struct. 35: 177-198.
J. P. DiNitto & D. G. Lambright (2006) "Membrane and juxtamembrane targeting by PH and PTB domains," 1761: 850-867.
F. M. Goi & A. Alonso (2006) "Biophysics of sphingolipids I. Membrane properties of sphingosine, ceramides and other simple sphingolipids," Biochim. Biophys. Acta 1758: 1902-1921.
B. Ramstedt & J. P. Slotte (2006) "Sphingolipids and the formation of sterol-enriched ordered membrane domains," Biochim. Biophysics. Acta 1758: 1945-1956.

Potential Test Questions:

1.a. Draw the structure of the phospholipid molecule phosphatidyl inositol. List (by name only) four compounds or groups that may substitute for inositol in other glycerophospholipids. What gives a glycerophospholipid like phosphatidyl inositol its amphipathic character? 
b. What type of modification to phosphatidylinositol makes it able to bind a protein with a pleckstrin homology domain to the surface of a membrane?

2.a. What distinguishes an integral protein from a peripheral membrane protein? Describe and explain what treatment may be required to extract an integral protein from a membrane and maintain it in solution. 
   b. Describe the structural motif that is most common in integral membrane proteins. Explain how this structure is ideally suited for a transmembrane segment. Describe and explain the commonly observed distribution of specific amino acid types along the bilayer-spanning protein segment. 

3.a. How is a hydropathy plot carried out? Explain what conclusions can be drawn from such a plot.
   b. Sketch hydropathy plots for proteins with either two or three transmembrane a-helices. For each of these proteins, draw a cartoon showing the predicted location of domains within and outside of the lipid bilayer, including locations of N-terminal and C-terminal domains. Briefly describe two ways in which the predicted location of these domains might be confirmed. 

Studio Exercise - Hydropathy Plot

The primary sequence for the erythrocyte integral membrane protein glycophorin is found in the Excel worksheet linked below (and in Fig. 12-21 p. 397). Engleman-Steitz-Goldman estimates of the free energy associated with transfer of each type of amino acid R-group from oil to water, in kJ/mol, are listed below. Generate your own hydropathy plot comparable to that shown in Fig. 12-22 on p. 397.
Use Excel to
sum the free energies of transfer of the 20-amino acid stretch beginning with each amino acid in the sequence, starting at the amino terminus (residue #1).
Plot this vs residue number. For example, the total free energy of transfer for amino acids #1-20 would be plotted against residue #1.

Excel Worksheet (click here)

Be prepared to answer and explain the following:

  • Why are values of DG for transfer of amino acid side chains from oil to water positive for some amino acids (e.g., Phe) and negative for other amino acids (e.g., Arg)?
  • What is implied by the finding of a single peak above 85 kJ/mol?
  • What experimental approaches could be used to confirm the transmembrane arrangement of the protein depicted in Figure 12-21 and in the cartoon at right, in which the N-terminal domain faces the outside of the red blood cell while the C-terminal domain contacts the cytosol.

DG for transferring amino acid side chains in a-helical polypeptides from oil to water, in kJ/mol:
Phe  15.5
Met  14.2
Ile  13.0
Leu  11.7
Val  10.9
Cys  8.4
Trp  7.9
Ala  6.7
Thr  5.0
Gly  4.2
Ser  2.5
Pro  -0.8
Tyr  -2.9
His  -12.6
Gln  -17.2
Asn  -20.1
Glu  -34.3
Lys  -36.8
Asp  -38.5
Arg  -51.5

Copyright 1998-2007 by Joyce J. Diwan. All rights reserved.

Lecture Notes on
Lipids & Membrane Structure

Interactive Quiz on   
Lipids & Membranes 

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