Binding of basic peptides to membranes produces lateral domains enriched in the acidic lipids phosphatidylserine and phosphatidylinositol 4,5-bisphosphate: an electrostatic model and experimental results
| Autor: | P. Luan, Michael Glaser, Stuart McLaughlin, G. Denisov, Stephen P Wanaski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Surface Properties Molecular Sequence Data Static Electricity Biophysics Peptide Phosphatidylserines 010402 general chemistry 01 natural sciences Biophysical Phenomena 03 medical and health sciences chemistry.chemical_compound Static electricity Phosphatidylinositol Amino Acid Sequence Binding site MARCKS Myristoylated Alanine-Rich C Kinase Substrate 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites Chemistry Ligand Intracellular Signaling Peptides and Proteins Membrane Proteins Proteins Models Theoretical Peptide Fragments 0104 chemical sciences Crystallography Kinetics Membrane 4-Chloro-7-nitrobenzofurazan Phosphatidylinositol 4 5-bisphosphate Microscopy Fluorescence Phosphatidylcholines Thermodynamics lipids (amino acids peptides and proteins) Research Article Protein Binding |
| Popis: | Direct fluorescence digital imaging microscopy observations demonstrate that a basic peptide corresponding to the effector region of the myristoylated alanine-rich C kinase substrate (MARCKS) self-assembles into membrane domains enriched in the acidic phospholipids phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). We show here that pentalysine, which corresponds to the first five residues of the MARCKS effector region peptide and binds to membranes through electrostatic interactions, also forms domains enriched in PS and PIP2. We present a simple model of domain formation that represents the decrease in the free energy of the system as the sum of two contributions: the free energy of mixing of neutral and acidic lipids and the electrostatic free energy. The first contribution is always positive and opposes domain formation, whereas the second contribution may become negative and, at low ionic strength, overcome the first contribution. Our model, based on Gouy-Chapman-Stern theory, makes four predictions: 1) multivalent basic ligands, for which the membrane binding is a steep function of the mole fraction of acidic lipid, form domains enriched in acidic lipids; domains break up at high concentrations of either 2) basic ligand or 3) monovalent salt; and 4) if multivalent anionic lipids (e.g., PIP2) are present in trace concentrations in the membrane, they partition strongly into the domains. These predictions agree qualitatively with experimental data obtained with pentalysine and spermine, another basic ligand. |
| Databáze: | OpenAIRE |
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