[en] Physical properties of membranes, such as fluidity, charge or curvature influence
their function. Proteins and peptides can modulate those properties and
conversely, the lipids can affect the activity and/or the structure of the
former. Tilted peptides are short hydrophobic protein fragments characterized by
an asymmetric distribution of their hydrophobic residues when helical. They were
detected in viral fusion proteins and in proteins involved in different
biological processes that need membrane destabilization. Those peptides and non
lamellar lipids such as PE or PA appear to cooperate in the lipid destabilization
process by enhancing the formation of negatively-curved domains. Such highly bent
lipidic structures could favour the formation of the viral fusion pore
intermediates or that of toroidal pores. Structural flexibility appears as
another crucial property for the interaction of peptides with membranes.
Computational analysis on another kind of lipid-interacting peptides, i.e. cell
penetrating peptides (CPP) suggests that peptides being conformationally
polymorphic should be more prone to traverse the bilayer. Future investigations
on the structural intrinsic properties of tilted peptides and the influence of
CPP on the bilayer organization using the techniques described in this chapter
should help to further understand the molecular determinants of the peptide/lipid
inter-relationships.
Weise K., and Reed J. Fusion peptides and transmembrane domains of fusion proteins are characterized by different but specific structural properties. Chembiochem 9 (2008) 934-943
Brasseur R., Lorge P., Goormaghtigh E., Ruysschaert J.M., Espion D., and Burny A. The mode of insertion of the paramyxovirus F1 N-terminus into lipid matrix, an initial step in host cell/virus fusion. Virus Genes 1 (1988) 325-332
Brasseur R., Vandenbranden M., Cornet B., Burny A., and Ruysschaert J.M. Orientation into the lipid bilayer of an asymmetric amphipathic helical peptide located at the N-terminus of viral fusion proteins. Biochim. Biophys. Acta 1029 (1990) 267-273
Efremov R.G., Nolde D.E., Volynsky P.E., Chernyavsky A.A., Dubovskii P.V., and Arseniev A.S. Factors important for fusogenic activity of peptides: molecular modeling study of analogs of fusion peptide of influenza virus hemagglutinin. Febs Lett. 462 (1999) 205-210
Lins L., Charloteaux B., Thomas A., and Brasseur R. Computational study of lipid-destabilizing protein fragments: towards a comprehensive view of tilted peptides. Proteins-Structure Function and Genetics 44 (2001) 435-447
Voneche V., Portelle D., Kettmann R., Willems L., Limbach K., Paoletti E., Ruysschaert J.M., Burny A., and Brasseur R. Fusogenic segments of bovine leukemia-virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target-cells. Proc. Natl. Acad. Sci. U. S. A. 89 (1992) 3810-3814
Adam B., Lins L., Stroobant V., Thomas A., and Brasseur R. Distribution of hydrophobic residues is crucial for the fusogenic properties of the Ebola virus GP2 fusion peptide. J. Virol. 78 (2004) 2131-2136
Martin I., Schaal H., Scheid A., and Ruysschaert J.M. Lipid membrane fusion induced by the human immunodeficiency virus type 1 gp41 N-terminal extremity is determined by its orientation in the lipid bilayer. J. Virol. 70 (1996) 298-304
Martin I., Dubois M.C., Defrisequertain F., Saermark T., Burny A., Brasseur R., and Ruysschaert J.M. Correlation between fusogenicity of synthetic modified peptides corresponding to the Nh2-terminal extremity of simian immunodeficiency virus Gp32 and their mode of insertion into the lipid bilayer- an infrared-spectroscopy study. J. Virol. 68 (1994) 1139-1148
Luneberg J., Martin I., Nussler F., Ruysschaert J.M., and Herrmann A. Structure and topology of the influenza-virus fusion peptide in lipid bilayers. J. Biol. Chem. 270 (1995) 27606-27614
Bradshaw J.P., Darkes M.J.M., Harroun T.A., Katsaras J., and Epand R.M. Oblique membrane insertion of viral fusion peptide probed by neutron diffractions. Biochemistry 39 (2000) 6581-6585
Han X., Bushweller J.H., Cafiso D.S., and Tamm L.K. Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin. Nat. Struct. Biol. 8 (2001) 715-720
Lai A.L., Park H., White J.M., and Tamm L.K. Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity. J. Biol. Chem. 281 (2006) 5760-5770
Brasseur R., Pillot T., Lins L., Vandekerckhove J., and Rosseneu M. Peptides in membranes: tipping the balance of membrane stability. Trends Biochem. Sci. 22 (1997) 167-171
Lins L., Flore C., Chapelle L., Talmud P.J., Thomas A., and Brasseur R. Lipid-interacting properties of the N-terminal domain of human apolipoprotein C-III. Protein Eng. 15 (2002) 513-520
Ravault S., Soubias O., Saurel O., Thomas A., Brasseur R., and Milon A. Fusogenic Alzheimer's peptide fragment A beta (29-42) in interaction with lipid bilayers: secondary structure, dynamics, and specific interaction with phosphatidyl ethanolamine polar heads as revealed by solid-state NMR. Protein Sci. 14 (2005) 1181-1189
Pillot T., Goethals M., Vanloo B., Talussot C., Brasseur R., Vandekerckhove J., Rosseneu M., and Lins L. Fusogenic properties of the C-terminal domain of the Alzheimer beta-amyloid peptide. J. Biol. Chem. 271 (1996) 28757-28765
Pillot T., Lins L., Goethals M., Vanloo B., Baert J., Vandekerckhove J., Rosseneu M., and Brasseur R. The 118-135 peptide of the human prion protein forms amyloid fibrils and induces liposome fusion. J. Mol. Biol. 274 (1997) 381-393
Crowet J.M., Lins L., Dupiereux I., Elmoualija B., Lorin A., Charloteaux B., Stroobant V., Heinen E., and Brasseur R. Tilted properties of the 67-78 fragment of alpha-synuclein are responsible for membrane destabilization and neurotoxicity. Proteins 68 (2007) 936-947
Lins L., and Brasseur R. Tilted peptides: a structural motif involved in protein membrane insertion?. J. Pept. Sci. 14 (2008) 416-422
Peuvot J., Schanck A., Lins L., and Brasseur R. Are the fusion processes involved in birth, life and death of the cell depending on tilted insertion of peptides into membranes?. J. Theor. Biol. 198 (1999) 173-181
Lins L., Charloteaux B., Heinen C., Thomas A., and Brasseur R. "De novo" design of peptides with specific lipid-binding properties. Biophy. J. 90 (2006) 470-479
Brasseur R. Tilted peptides: a motif for membrane destabilization (hypothesis). Mol. Membr. Biol. 17 (2000) 31-40
Brasseur R. Differentiation of lipid-associating helices by use of three-dimensional molecular hydrophobicity potential calculations. J. Biol. Chem. 266 (1991) 16120-16127
Harris F., Wallace J., and Phoenix D.A. Use of hydrophobic moment plot methodology to aid the identification of oblique orientated alpha-helices. Mol. Membr. Biol. 17 (2000) 201-207
Lorin A., Thomas A., Stroobant V., Brasseur R., and Lins L. Lipid-destabilising properties of a peptide with structural plasticity. Chem. Phys. Lipids 141 (2006) 185-196
Lambert G., Decout A., Vanloo B., Rouy D., Duverger N., Kalopissis A., Vadekerckhove J., Chambaz J., Brasseur R., and Rosseneu M. The C-terminal helix of human apolipoprotein AII promotes the fusion of unilamellar liposomes and displaces apolipoprotein AI from high-density lipoproteins. Eur. J. Biochem. 253 (1998) 328-338
Charloteaux B., Lorin A., Crowet J.M., Stroobant V., Lins L., Thomas A., and Brasseur R. The N-terminal 12 residue long peptide of HIV gp41 is the minimal peptide sufficient to induce significant T-cell-like membrane destabilization in vitro. J. Mol. Biol. 359 (2006) 597-609
Lorin A., Lins L., Stroobant V., Brasseur R., and Charloteaux B. Determination of the minimal fusion peptide of bovine leukemia virus gp30. Biochem. Biophys. Res. Commun. 355 (2007) 649-653
Lorin A., Lins L., Stroobant V., Brasseur R., and Charloteaux B. The minimal fusion peptide of simian immunodeficiency virus corresponds to the 11 first residues of gp32. J. Pept. Sci. 14 (2008) 423-428
Horth M., Lambrecht B., Khim M.C.L., Bex F., Thiriart C., Ruysschaert J.M., Burny A., and Brasseur R. Theoretical and functional-analysis of the SIV fusion peptide. Embo J. 10 (1991) 2747-2755
Brasseur R. TAMMO: Theoretical Analysis of Membrane Molecular Organisation. In: Brasseur R. (Ed). Molecular Description of Biological Membrane Components by Computer-Aided Conformational Analysis (1990), CRC Press, Boca Raton 203-219
Lins L., Flore C., Chapelle L., Talmud P.J., Thomas A., and Brasseur R. Lipid-interacting properties of the N-terminal domain of human apolipoprotein C-III. Protein Eng. 15 (2002) 513-520
Davies S.M., Epand R.F., Bradshaw J.P., and Epand R.M. Modulation of lipid polymorphism by the feline leukemia virus fusion peptide: implications for the fusion mechanism. Biochemistry 37 (1998) 5720-5729
Mingeot-Leclercq M.P., Lins L., Bensliman M., Van Bambeke F., Van der Smissen P., Peuvot J., Schanck A., and Brasseur R. Membrane destabilization induced by beta-amyloid peptide 29-42: importance of the amino-terminus. Chem. Phys. Lipids 120 (2002) 57-74
El Kirat K., Dufrene Y.F., Lins L., and Brasseur R. The SIV tilted peptide induces cylindrical reverse micelles in supported lipid bilayers. Biochemistry 45 (2006) 9336-9341
El Kirat K., Lins L., Brasseur R., and Dufrene Y.F. Fusogenic tilted peptides induce nanoscale holes in supported phosphatidylcholine bilayers. Langmuir 21 (2005) 3116-3121
Mingeot-Leclercq M.P., Lins L., Bensliman M., Thomas A., Van Bambeke F., Peuvot J., Schanck A., and Brasseur R. Piracetam inhibits the lipid-destabilising effect of the amyloid peptide A beta C-terminal fragment. Biochim. Biophys. Acta, Biomembr. 1609 (2003) 28-38
Chernomordik L.V., Leikina E., Frolov V., Bronk P., and Zimmerberg J. An early stage of membrane fusion mediated by the low pH conformation of influenza hemagglutinin depends upon membrane lipids. J. Cell Biol. 136 (1997) 81-93
Yang L., and Huang H.W. Observation of a membrane fusion intermediate structure. Science 297 (2002) 1877-1879
Siegel D.P. The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion. Biophy. J. 76 (1999) 291-313
Lins L., El Kirat K., Charloteaux B., Flore C., Stroobant V., Thomas A., Dufrene Y., and Brasseur R. Lipid-destabilizing properties of the hydrophobic helices H8 and H9 from colicin E1. Mol. Membr. Biol. 24 (2007) 419-430
Sobko A.A., Kotova E.A., Antonenko Y.N., Zakharov S.D., and Cramer W.A. Effect of lipids with different spontaneous curvature on the channel activity of colicin E1: evidence in favor of a toroidal pore. Febs Lett. 576 (2004) 205-210
Zakharov S.D., Kotova E.A., Antonenko Y.N., and Cramer W.A. On the role of lipid in colicin pore formation. Biochim. Biophys. Acta 1666 (2004) 239-249
Epand R.F., Martinou J.C., Montessuit S., Epand R.M., and Yip C.M. Direct evidence for membrane pore formation by the apoptotic protein Bax. Biochem. Biophys. Res. Commun. 298 (2002) 744-749
Basanez G., Sharpe J.C., Galanis J., Brandt T.B., Hardwick J.M., and Zimmerberg J. Bax-type apoptotic proteins porate pure lipid bilayers through a mechanism sensitive to intrinsic monolayer curvature. J. Biol. Chem. 277 (2002) 49360-49365
Garcia-Saez A.J., Coraiola M., Dalla Serra M., Mingarro I., Menestrina G., and Salgado J. Peptides derived from apoptotic Bax and Bid reproduce the poration activity of the parent full-length proteins. Biophys. J. 88 (2005) 3976-3990
Garcia-Saez A.J., Coraiola M., Serra M.D., Mingarro I., Muller P., and Salgado J. Peptides corresponding to helices 5 and 6 of Bax can independently form large lipid pores. FEBS J. 273 (2006) 971-981
Garcia-Saez A.J., Chiantia S., Salgado J., and Schwille P. Pore formation by a Bax-derived peptide: effect on the line tension of the membrane probed by AFM. Biophys. J. 93 (2007) 103-112
Matsuzaki K., Mitani Y., Akada K.Y., Murase O., Yoneyama S., Zasloff M., and Miyajima K. Mechanism of synergism between antimicrobial peptides magainin 2 and PGLa. Biochemistry 37 (1998) 15144-15153
Allende D., Simon S.A., and McIntosh T.J. Melittin-induced bilayer leakage depends on lipid material properties: evidence for toroidal pores. Biophys. J. 88 (2005) 1828-1837
Gordon L.M., Mobley P.W., Pilpa R., Sherman M.A., and Waring A.J. Conformational mapping of the N-terminal peptide of HIV-1 gp41 in membrane environments using C-13-enhanced Fourier transform infrared spectroscopy. Biochim. Biophys. Acta, Biomembr. 1559 (2002) 96-120
Gordon L.M., Curtain C.C., Zhong Y.C., Kirkpatrick A., Mobley P.W., and Waring A.J. The amino-terminal peptide of HIV-1 glycoprotein-41 interacts with human erythrocyte-membranes- peptide conformation, orientation and aggregation. Biochim. Biophys. Acta 1139 (1992) 257-274
Jaroniec C.P., Kaufman J.D., Stahl S.J., Viard M., Blumenthal R., Wingfield P.T., and Bax A. Structure and dynamics of micelle-associated human immunodeficiency virus gp41 fusion domain. Biochemistry 44 (2005) 16167-16180
Pereira F.B., Goni F.M., Muga A., and Nieva J.L. Permeabilization and fusion of uncharged lipid vesicles induced by the HIV-1 fusion peptide adopting an extended conformation: dose and sequence effects. Biophy. J. 73 (1997) 1977-1986
Rafalski M., Lear J.D., and Degrado W.F. Phospholipid interactions of synthetic peptides representing the N-terminus of HIV Gp41. Biochemistry 29 (1990) 7917-7922
Sackett K., and Shai Y. The HIV fusion peptide adopts intermolecular parallel beta-sheet structure in membranes when stabilized by the adjacent N-terminal heptad repeat: a C-13 FTIR study. J. Mol. Biol. 350 (2005) 790-805
Yang J., Gabrys C.M., and Weliky D.P. Solid-state nuclear magnetic resonance evidence for an extended beta strand conformation of the membrane-bound HIV-1 fusion peptide. Biochemistry 40 (2001) 8126-8137
Yang R., Yang J., and Weliky D.P. Synthesis, enhanced fusogenicity, and solid state NMR measurements of cross-linked HIV-1 fusion peptides. Biochemistry 42 (2003) 3527-3535
Yang R., Prorok M., Castellino F.J., and Weliky D.P. A trimeric HIV-1 fusion peptide construct which does not self-associate in aqueous solution and which has 15-fold higher membrane fusion rate. J. Am. Chem. Soc. 126 (2004) 14722-14723
Peisajovich S.G., Epand R.F., Pritsker M., Shai Y., and Epand R.M. The polar region consecutive to the HIV fusion peptide participates in membrane fusion. Biochemistry 39 (2000) 1826-1833
Wexler-Cohen Y., Sackett K., and Shai Y. The role of the N-terminal heptad repeat of HIV-1 in the actual lipid mixing step as revealed by its substitution with distant coiled coils. Biochemistry 44 (2005) 5853-5861
Korazim O., Sackett K., and Shai Y. Functional and structural characterization of HIV-1 gp41 ectodomain regions in phospholipid membranes suggests that the fusion-active conformation is extended. J. Mol. Biol. 364 (2006) 1103-1117
Castano S., and Desbat B. Structure and orientation study of fusion peptide FP23 of gp41 from HIV-1 alone or inserted into various lipid membrane models (mono-, bi- and multibi-layers) by FT-IR spectroscopies and Brewster angle microscopy. Biochim. biophys. acta, Biomembr. 1715 (2005) 81-95
Gordon L.M., Mobley P.W., Lee W., Eskandari S., Kaznessis Y.N., Sherman M.A., and Waring A.J. Conformational mapping of the N-terminal peptide of HIV-1 gp41 in lipid detergent and aqueous environments using C-13-enhanced Fourier transform infrared spectroscopy. Protein Sci. 13 (2004) 1012-1030
Saez-Cirion A., and Nieva J.L. Conformational transitions of membrane-bound HIV-1 fusion peptide. Biochim. Biophys. Acta, Biomembr. 1564 (2002) 57-65
Buzon V., Padros E., and Cladera J. Interaction of fusion peptides from HIV gp41 with membranes: a time-resolved membrane binding, lipid mixing, and structural study. Biochemistry 44 (2005) 13354-13364
Martin I., Defrisequertain F., Decroly E., Vandenbranden M., Brasseur R., and Ruysschaert J.M. Orientation and structure of the Nh2-terminal HIV-1 Gp41 peptide in fused and aggregated liposomes. Biochim. Biophys. Acta 1145 (1993) 124-133
Tamm L.K., Lai A.L., and Li Y. Combined NMR and EPR spectroscopy to determine structures of viral fusion domains in membranes. Biochim. Biophys. Acta 1768 (2007) 3052-3060
Foerg C., and Merkle H.P. On the biomedical promise of cell penetrating peptides: limits versus prospects. J. Pharm. Sci. 97 (2008) 144-162
Mae M., and Langel U. Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery. Curr. Opin. Pharmacol. 6 (2006) 509-514
Dietz G.P., and Bahr M. Delivery of bioactive molecules into the cell: the Trojan horse approach. Mol. Cell. Neurosci. 27 (2004) 85-131
Fawell S., Seery J., Daikh Y., Moore C., Chen L.L., Pepinsky B., and Barsoum J. Tat-mediated delivery of heterologous proteins into cells. Proc. Natl. Acad. Sci. U. S. A. 91 (1994) 664-668
Derossi D., Chassaing G., and Prochiantz A. Trojan peptides: the penetratin system for intracellular delivery. Trends Cell Biol. 8 (1998) 84-87
Pooga M., Hallbrink M., Zorko M., and Langel U. Cell penetration by transportan. FASEB J. 12 (1998) 67-77
Morris M.C., Depollier J., Mery J., Heitz F., and Divita G. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat. Biotechnol. 19 (2001) 1173-1176
Morris M.C., Vidal P., Chaloin L., Heitz F., and Divita G. A new peptide vector for efficient delivery of oligonucleotides into mammalian cells. Nucleic Acids Res. 25 (1997) 2730-2736
Wyman T.B., Nicol F., Zelphati O., Scaria P.V., Plank C., and Szoka Jr. F.C. Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers. Biochemistry 36 (1997) 3008-3017
Derossi D., Calvet S., Trembleau A., Brunissen A., Chassaing G., and Prochiantz A. Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J. Biol. Chem. 271 (1996) 18188-18193
Binder H., and Lindblom G. Charge-dependent translocation of the Trojan peptide penetratin across lipid membranes. Biophys. J. 85 (2003) 982-995
Deshayes S., Morris M.C., Divita G., and Heitz F. Interactions of amphipathic CPPs with model membranes. Biochim. Biophys. Acta 1758 (2006) 328-335
Henriques S.T., and Castanho M.A. Consequences of nonlytic membrane perturbation to the translocation of the cell penetrating peptide pep-1 in lipidic vesicles. Biochemistry 43 (2004) 9716-9724
Jones A.T. Macropinocytosis: searching for an endocytic identity and role in the uptake of cell penetrating peptides. J. Cell. Mol. Med. 11 (2007) 670-684
Kaplan I.M., Wadia J.S., and Dowdy S.F. Cationic TAT peptide transduction domain enters cells by macropinocytosis. J. Control. Release 102 (2005) 247-253
Richard J.P., Melikov K., Brooks H., Prevot P., Lebleu B., and Chernomordik L.V. Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors. J. Biol. Chem. 280 (2005) 15300-15306
Letoha T., Gaal S., Somlai C., Czajlik A., Perczel A., and Penke B. Membrane translocation of penetratin and its derivatives in different cell lines. J. Mol. Recognit. 16 (2003) 272-279
Fischer R., Fotin-Mleczek M., Hufnagel H., and Brock R. Break on through to the other side-biophysics and cell biology shed light on cell-penetrating peptides. Chembiochem. 6 (2005) 2126-2142
Magzoub M., Eriksson L.E., and Graslund A. Conformational states of the cell-penetrating peptide penetratin when interacting with phospholipid vesicles: effects of surface charge and peptide concentration. Biochim. Biophys. Acta 1563 (2002) 53-63
Chaloin L., Vidal P., Heitz A., Van Mau N., Mery J., Divita G., and Heitz F. Conformations of primary amphipathic carrier peptides in membrane mimicking environments. Biochemistry 36 (1997) 11179-11187
Deshayes S., Decaffmeyer M., Brasseur R., and Thomas A. Structural polymorphism of two CPP: an important parameter of activity. Biochim. Biophys. Acta 1778 (2008) 1197-1205
Thomas A., Deshayes S., Decaffmeyer M., Van Eyck M.H., Charloteaux B., and Brasseur R. Prediction of peptide structure: how far are we?. Proteins 65 (2006) 889-897
Etchebest C., Benros C., Hazout S., and de Brevern A.G. A structural alphabet for local protein structures: improved prediction methods. Proteins 59 (2005) 810-827
Soomets U., Lindgren M., Gallet X., Hallbrink M., Elmquist A., Balaspiri L., Zorko M., Pooga M., Brasseur R., and Langel U. Deletion analogues of transportan. Biochim. Biophys. Acta, Biomembr. 1467 (2000) 165-176
Lindberg M., Biverstahl H., Graslund A., and Maler L. Structure and positioning comparison of two variants of penetratin in two different membrane mimicking systems by NMR. Eur. J. Biochem. 270 (2003) 3055-3063
