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Erwin London, Ph.D.


Department of Biochemistry and Cell Biology

Center for Structural Biology
Centers for Molecular Medicine
Stony Brook University
Stony Brook, NY 11794-5215

Office telephone: 631-632-8564
Fax: 631-632-8575


  • Research Description
    Membrane Protein Structure: Determining the Rules for Protein Behavior in Membranes.

            Our group is studying membrane protein structure and function by combining spectroscopic methods, such as fluorescence, with chemical, biochemical, immunochemical and molecular biological approaches. We are interested in the determining membrane protein structure and the origin of specific lipid-protein and protein-protein interactions.   We have studied the relationship between amino acid sequence and structure using simple transmembrane helices. Such helices are the main structural element within membrane proteins. Their structure and location within the bilayer is analyzed using fluorescence, fluorescence quenching, circular dichroism and other spectroscopic techniques. These studies are allow us to derive basic rules for membrane protein folding and protein movement across membranes.

    The Structure and Function of Cholesterol-Rich Membrane Domains

          Together with Dr. Deborah Brown in the Dept. Of Biochemistry and Cell Biology we have been studying the structure and function of lipid domains enriched in cholesterol and sphingolipid. These domains have been proposed to have a functional role in processes such as viral and toxin entry into cells, protein sorting among organelles, signal transduction, prion formation and amyloid formation. Our studies involve determining the basic principles that drive the formation of these domains and regulate their lipid and protein composition.   One project involves domains in bacteria, including (in collaboration with Dr. Jorge Benach, Dept. of Molecular Genetics and Microbiology) Borrelia burgdorferi, the bacterium that is the cause of Lyme disease.  We are also carrying out studies on these domains in mammalian cells.

           The principles of membrane domains formation can also be studied in artificial lipid vesicles.   A limitation of using artificial membranes has been that they lack lipid asymmetry, the difference in lipid composition in their inner and outer layers found in many natural membranes.  We have developed a method to prepare asymmetric artificial vesicles that closely mimic natural membrane, and are applying the methodology to analyze the rules for domain formation in natural membranes.

  • Publications
    1. Asuncion-Punzalan, E., and London, E. (1995) "Control of the Depth of Molecules within Membranes by Polar Groups: Determination of the Location of Anthracene Labeled Probes in Model Membranes by Parallax Analysis of Nitroxide-Labeled Phospholipid Induced Fluorescence Quenching" Biochemistry 34, 11460-11466. 
    2. Tortorella, D., Sesardic, D., Dawes, C.S., and London, E. (1995) "Immunochemical Analysis of the Structure of Diphtheria Toxin Shows All Three Domains Undergo Structural Changes at Low pH" J. Biol. Chem. 270, 27439-27445.
    3. Tortorella, D., Sesardic, D., Dawes, C.S., and London, E. (1995) "Immunochemical Analysis of the Structure of Diphtheria Toxin Shows All Three Domains Penetrate Across Model Membranes" J. Biol. Chem. 270, 27446-27452.
    4. Kachel, K., Asuncion-Punzalan, E., and London, E. (1995) "Anchoring of Trp and Tyr Analogs at the Hydrocarbon-Polar Boundary in Membranes: Parallax Analysis of Fluorescence Quenching Induced by Nitroxide-Labeled Phospholipids" Biochemistry 34, 15475-15479.
    5. Paliwal, R., and London, E. (1996) "Comparison of the Conformation, Hydrophobicity and Model Membrane Interaction of Diphtheria Toxin to That of Formaldehyde-Treated Toxin (Diphtheria Toxoid): Formaldehyde Stabilization of the Native Conformation Inhibits Changes That Allow Membrane Insertion", Biochemistry 35, 2374-2379.
    6. Ren, J., Lew, S., Wang, Z., and London, E. (1997) "Transmembrane Orientation of Hydrophobic -Helices is Regulated by the Relationship of Helix Length to Bilayer Thickness and by Cholesterol Concentration", Biochemistry 36, 10213-10220.
    7. Ahmed, S.N., Brown, D.A., and London, E. (1997) "On the Origin of Sphingolipid/Cholesterol Rich Detergent-Insoluble Domains in Cell Membranes: Physiological Concentrations of Cholesterol and Sphingolipid Induce Formation of a Detergent-Insoluble Liquid Ordered Phase in Model Membranes", Biochemistry 36, 10944-10953.
    8. Wang, Y., Malenbaum, S.E., Kachel, K., Zhan, H., Collier, R.J., and London, E. (1997) "Identification of Shallow and Deep Membrane Penetrating Conformations of Diphtheria Toxin T Domain That Are Regulated by T Domain Concentration and Bilayer Width", J. Biol. Chem. 272, 25091-25098.
    9. Wang, Y., Kachel, K., Pablo, L., and London, E. (1997) "Use of Trp Mutations to Evaluate the Conformational Behavior and Membrane-Insertion of A and B Chains in Whole Diphtheria Toxin", Biochemistry 36, 13600-13608.
    10. Schroeder, R., Ahmed, S.N., Zhu, Y., London, E., and Brown, D.A. (1998) "How Cholesterol and Sphingolipid Enhance the Triton X-100-Insolubility of GPI-Anchored Proteins by Promoting Formation of Detergent-Insoluble Ordered Membrane Domains", J. Biol. Chem. 273, 1150-1157.
    11. Asuncion-Punzalan, E., Kachel, K., and London, E. (1998) "Polar Molecules Can Locate at Both Shallow and Deep Locations in Membranes: The Behavior of Dansyl and Related Probes", Biochemistry 37, 4603-4611.
    12. Kaiser, R.D., and London, E. (1998) "Location of Diphenylhexatriene (DPH) Derivatives Within Membranes: Comparison of Different Fluorescence Quenching Analyses of Membrane Depth", Biochemistry 37, 8180-8190. (Review) Brown, D.A., and London, E. (1998) "Origin and Structure of Ordered Lipid Domains in Biological Membranes" J. Memb. Bio. 164, 103-114.
    13. Brown, D.A., and London, E. (1998) "Functions of Lipid Rafts in Biological Membranes", Ann. Rev. Cell Dev. Bio. 14, 111-136.
    14. Kachel, K., Asuncion-Punzalan, E., and London, E. (1998) "The Location of Molecules with Charged Groups in Membranes", Biochim. Biophys. Acta 1374, 63-76. 
    15. Kachel, K., Ren, J., Collier, R.J., and London, E. (1998) "Identifying Transmembrane States and Defining the Membrane Insertion Boundaries of Hydrophobic Helices: The Conformation of TH8 and TH9 in Membrane-Inserted Diphtheria Toxin T Domain", J. Biol. Chem. 273, 22950-22956.
    16. Malenbaum, S.E., Collier, R.J., and London, E. (1998) "Membrane Insertion of Helices TH1, TH5 and TH9 of the T Domain of Diphtheria Toxin Probed With Single Trp Mutants", Biochemistry 37, 17915-17922.
    17. Ren, J., Collier, R.J., and London, E. (1999) "Role of Ionizable Residues at the Tips of Hydrophobic Helices in the Transmembrane Insertion of the T Domain of Diphtheria Toxin", Biochemistry 38, 976-984.
    18. Ren, J., Lew, S., Wang, J., and London, E. (1999) "Control of Transmembrane Orientation and Interhelical Interactions within Membranes by Hydrophobic Helix Length", Biochemistry 38, 5905-5912.
    19. Ren, J., Kachel, K., Malenbaum, S.E., Collier, R.J. and London, E. (1999) "Interaction of Diphtheria Toxin T Domain with Molten Globule Like Proteins and Its Implications for Translocation", Science 284, 955-957.
    20. Sharpe, J.C., and London, E. (1999) "Diphtheria Toxin Forms Pores of Different Sizes Depending On Its Concentration in Membranes: Probable Relationship to Oligomerization", J. Memb. Biol. 171, 209-221.
    21. Sharpe, J.C., Kachel, K., and London, E. (1999), The Effects of Inhibitors Upon Pore Formation by Diphtheria Toxin and Diphtheria Toxin T Domain", J. Memb. Biol. 171, 223-233.
    22. Xu, X., and London, E. (2000) "The Effect of Sterol Structure on Membrane Lipid Domains Reveals How Cholesterol Can Induce Lipid Domain Formation", Biochemistry 39, 844-849. 70. Xu, X., and London, E. (2000) "The Effect of Sterol Structure on Membrane Lipid Domains Reveals How Cholesterol Can Induce Lipid Domain Formation" Biochemistry 39, 844-849.
    23. Brown, D.A., and London, E. (2000) "Structure and Function of Sphingolipid- and Cholesterol-rich Rafts" J. Biol. Chem. 275, 17221-17224. 
    24. Lew, S., and London, E. (2000) "The Effect of Polar/Ionizable Residues Within the Core of Hydrophobic Helices on Their Behavior Within Lipid Bilayers" Biochemistry39, 9632-9640.
    25. London, E., Brown, D.A., and Xu, X. (2000) "Fluorescence Quenching Assay of Sphingolipid/Phospholipid Phase Separation" Meth. Enzymol. 312, 272-290.
    26. London, E., and Brown, D.A. (2000) "Insolubility of Lipids in Triton X-100: Physical Origin and Relationship to Sphingolipid/Cholesterol Membrane Domains (rafts)" Biochim. Biophys. Acta 1508, 182-195. Xu, X., Bittman, R., Duportail, G.,
    27. Heissler, D., Vilcheze, C., and London, E. (2001) "Effect of the Structure of Natural Sterols and Sphingolipids on the Formation of Ordered Sphingolipid/Sterol Domains (Rafts): Comparison of Cholesterol to Plant, Fungal and Disease-Associated Sterols, and Comparison of Sphingomyelin, Cerebrosides and Ceramide" J. Biol. Chem. 276, 33540-33546.
    28. London, E., and Ladokhin, A.S. (2002) "Measuring the Depth of Amino Acid Residues in Membrane-Inserted Peptides by Fluorescence Quenching" in Current Topics in Membranes: Peptide-Lipid Interactions (Simon, S.A., and McIntosh, T.J. Eds.) Vol. 52 Academic Press, 89-115.
    29. Hammond, K., Caputo, G.A., and London, E. (2002) "Interaction of the Membrane-Inserted Diphtheria Toxin T Domain with Peptides and Its Possible Implications for Chaperone-like T Domain Behavior" Biochemistry 41, 3243-3253.
    30. Rosconi, M.P., and London, E. (2002) "Topography of Helices 5-7 in Membrane- Inserted Diphtheria Toxin T Domain: Identification and Insertion Boundaries of Two Hydrophobic Sequences That Do Not Form a Stable Transmembrane Hairpin" J. Biol.Chem., 277, 16517-16527.
    31. London, E. (2002) "Insights into Lipid Domain/Raft Structure and Formation from Experiments in Model Membranes" Curr. Opin. Struct. Bio., 12, 480-486.
    32. Caputo, G.A., and London, E. (2003) "Using a Novel Dual Fluorescence Quenching Assay for Measurement of Trp Depth Within Lipid Bilayers to Determine Hydrophobic Alpha-Helix Locations Within Membranes" Biochemistry, in press
    33. Caputo, G.A., and London, E. (2003) "Cumulative Effects of Amino Acid Substitutions and Hydrophobic Mismatch Upon the Transmembrane Stability and Conformation of Hydrophobic Alpha-Helices" Biochemistry, in press
    34. Son, M., and London, E. (2013) “The Dependence of Lipid Asymmetry Upon Phosphatidylcholine Acyl Chain Structure” J. Lipid Res. 54, 223-231.
    35. Lin, Q. and London E. (2013) “Altering hydrophobic sequence lengths shows that hydrophobic mismatch controls affinity for ordered lipid domains (rafts) in the multi-transmembrane strand protein perfringolysin O”,  J. Biol. Chem., 288, 1340–1352.
    36. Chiantia, S. and London, E. (2013) “Lipid Bilayer Asymmetry” in Encyclopedia of Biophysics 2nd ed (Roberts. G.C.K. Ed.)  Springer-Verlag. Heidelberg: Berlin, pp. 1250-1253.
    37. Caputo, G.A. and London, E. (2013) “Analyzing transmembrane protein and hydrophobic helix topography by dual fluorescence quenching” in Methods in Molecular Biology series Volume 974, Lipid-Protein Interactions: Methods and  Protocols (Kleinschmidt, J.H. Ed.) Humana Press/Springer, New York, pp. 279-295.
    38. Crowley, J.T. Toledo, A.M., LaRocca, T.J., Coleman, J.L., London, E., and Benach, J.L. (2013) “Lipid Exchange between Borrelia burgdorferi and host cells” PLoS Pathogens, 9, e1003109.
    39. Chiantia, S., and London, E. (2013) “Sphingolipids and Membrane Domains: Recent Advances” in Handbook of Experimental Pharmacology: Sphingolipids  in Health and Disease (Gulbins, E., and Petrache, I. Eds.)  Volume 215, pp 33-55 Springer, New York
    40. LaRocca, T.J., Pathak, P., Chiantia, S., Toledo, A., Silvius, J.R., Benach, J.L. and London, E. (2013) “Proving Lipid Rafts Exist: Membrane Domains in the Prokaryote Borrelia burgdorferi Have the Same Properties as Eukaryotic Lipid Rafts” PLoS Pathogens, 9, e1003353.
    41. Su, C.-Y., London, E., and Sampson, N.S. (2013) “Mapping peptide thiol accessibility in membranes using a quarternary ammonium isotope-coded mass tag (ICMT)” Bioconjugate Chemistry  24, 1235-1247.
    42. Son, M., and London, E. (2013) “The Dependence of Lipid Asymmetry Upon Polar Headgroup Structure” J. Lipid Res., 54, 3385-3393.  
    43. Huang, Z., and London, E. (2013) “Effect of Cyclodextrin and Membrane Lipid Structure upon Cyclodextrin-Lipid Interaction” Langmuir 29, 14631-14638.
    44. Lin, Q., and London, E. (2013) “Transmembrane Protein (Perfringolysin O) Association with Ordered Membrane Domains (Rafts) Depends Upon the Raft-Associating Properties of the Protein-Bound Sterol” Biophys. J., 105, 2733-2742.
    45. Lin, Q., and London, E. (2014) “Preparation of Artificial Plasma Membrane Mimicking Vesicles With Lipid Asymmetry” PLoS ONE 9, e87903.
    46. Lin, Q., and London, E. (2014) “The Influence of Lipid Asymmetry Upon the Conformation of a Membrane-Inserted Protein (Perfringolysin O)” J. Biol. Chem. 289, 5467–5478.
    47. Toledo, A., Crowley, J.T., Coleman, J.L., LaRocca, T.J., Chiantia, S., London, E., and Benach, J.L. (2014) “Selective Association of the Outer Surface Lipoproteins With the Lipid Rafts of Borrelia burgdorferi”, mBio 5, e00899-14.  
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