Hydrogen bonding and binding of polybasic residues with negatively charged mixed lipid monolayers

TitleHydrogen bonding and binding of polybasic residues with negatively charged mixed lipid monolayers
Publication TypeJournal Article
Year of Publication2008
AuthorsLorenz CD, Faraudo J, Travesset A
Journal TitleLangmuir
Volume24
Pages1654-1658
Date PublishedMar
Type of ArticleArticle
ISBN Number0743-7463
Accession NumberISI:000253460200017
Keywords5-BISPHOSPHATE, BASIC PEPTIDES, C-KINASE SUBSTRATE, ELECTROSTATIC SEQUESTRATION, FORCE-FIELD, MOLECULAR-DYNAMICS SIMULATION, phosphatidic-acid, PHOSPHATIDYLINOSITOL 4, phospholipid-membranes, PLASMA-MEMBRANE, proteins
Abstract

Phosphoinositides, phosphorylated products of phosphatidylinositol, are a family of phospholipids present in tiny amounts (1% or less) in the cytosolic surface of cell membranes, yet they play an astonishingly rich regulatory role, particularly in signaling processes. In this letter, we use molecular dynamics simulations on a model system of mixed lipid monolayers to investigate the interaction of phosphatidylinositol 4,5-bisphosphate (PIP2) the most common of the phosphoinositides, with a polybasic peptide consisting of 13 lysines. Our results show that the polybasic peptide sequesters three PIP2 molecules, forming a complex stabilized by the formation of multiple hydrogen bonds between PIP2 and the Lys residues. We also show that the polybasic peptide does not sequester other charged phospholipids such as phosphatidylserine because of the inability to form long-lived stable hydrogen bonds.

DOI10.1021/la703550t
Alternate JournalLangmuir