title: Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions.
abstract: Basic amino acids play a key role in the binding of membrane associated proteins to negatively charged membranes. However, side chains of basic amino acids like lysine do not only provide a positive charge, but also a flexible hydrocarbon spacer that enables hydrophobic interactions. We studied the influence of hydrophobic contributions to the binding by varying the side chain length of pentapeptides with ammonium groups starting with lysine to lysine analogs with shorter side chains, namely omithine (Orn), alpha, gamma-diaminobutyric acid (Dab) and alpha, beta-diaminopropionic acid (Dap). The binding to negatively charged phosphatidylglycerol (PG) membranes was investigated by calorimetry, FT-infrared spectroscopy (FT-IR) and monolayer techniques. The binding was influenced by counteracting and sometimes compensating contributions. The influence of the bound peptides on the lipid phase behavior depends on the length of the peptide side chains. Isothermal titration calorimetry (ITC) experiments showed exothermic and endothermic effects compensating to a different extent as a function of side chain length. The increase in lipid phase transition temperature was more significant for peptides with shorter side chains. FTIR-spectroscopy revealed changes in hydration of the lipid bilayer interface after peptide binding. Using monolayer techniques, the contributions of electrostatic and hydrophobic effects could clearly be observed. Peptides with short side chains induced a pronounced decrease in surface pressure of PG monolayers whereas peptides with additional hydrophobic interactions decreased the surface pressure much less or even lead to an increase, indicating insertion of the hydrophobic part of the side chain into the lipid monolayer.
authors.affiliation: Institute of Chemistry, Martin-Luther-University Halle-Wittenberg, von-Danckelmoann-Platz 4, D-06120 Halle (Saale), Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Hoernke
authors.forename: Christian
authors.initials: C
authors.lastname: Schwieger
authors.forename: Andreas
authors.initials: A
authors.lastname: Kerth
authors.forename: Alfred
authors.initials: A
authors.lastname: Blume
mesh_terms: D000599:Amino Acids, Diamino / Q000737:chemistry / Q000378:metabolism; D000613:Aminobutyrates / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002151:Calorimetry / Q000379:methods; D002152:Calorimetry, Differential Scanning; D002412:Cations / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D009952:Ornithine / Q000737:chemistry / Q000378:metabolism; D044367:Phase Transition; D010715:Phosphatidylglycerols / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D044366:Transition Temperature
chemical_list: D000599:Amino Acids, Diamino; D000613:Aminobutyrates; D002412:Cations; D008051:Lipid Bilayers; D008563:Membrane Lipids; D009842:Oligopeptides; D010715:Phosphatidylglycerols; C100126:oxalyldiaminopropionic acid; C005959:2,4-diaminobutyric acid; D009952:Ornithine; D008239:Lysine