Search our Database of Scientific Publications and Authors

I’m looking for a
    Langevin dynamics simulations of charged model phosphatidylinositol lipids in the presence of diffusion barriers: toward an atomic level understanding of corralling of PIP2 by protein fences in biological membranes.
    BMC Biophys 2014 26;7:13. Epub 2014 Nov 26.
    Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD USA.
    Background: The polyvalent acidic lipid phosphatidylinositol, 4,5-bisphosphate (PIP2) is important for many cellular functions. It has been suggested that different pools of PIP2 exist in the cytoplasmic leaflet of the plasma membrane, and that such pooling could play a role in the regulation of PIP2. The mechanism of fencing, however, is not understood.

    Results: This study presents the results of Langevin dynamics simulations of PIP2 to elucidate some of the molecular level considerations that must be applied to models for fencing. For each simulation, a pool of PIP2 (modeled as charged spheres) was placed in containments with boundaries modeled as a single row of rods (steric or electrostatic) or rigid protein filaments. It is shown that even a small gap (20 Å, which is 1.85 times larger than the diameter of a PIP2 sphere) leads to poor steric blocking, and that electrostatic blockage is only effective at very high charge density. Filaments of human septin, yeast septin, and actin also failed to provide adequate blockage when placed on the membrane surface. The two septins do provide high blockage consistent with experiment and with phenomenological considerations of permeability when they are buried 9 Å and 12 Å below the membrane surface, respectively. In contrast, burial does not improve blockage by the "arch-shaped" actin filaments. Free energy estimates using implicit membrane-solvent models indicate that burial of the septins to about 10 Å can be achieved without penetration of charged residues into the hydrophobic region of the membrane.

    Conclusions: These results imply that a functioning fence assembled from protein filaments must either be buried well below the membrane surface, have more than a single row, or contain additional components that fill small gaps in the filaments.

    Similar Publications

    Interactions of the EGFR juxtamembrane domain with PIP2-containing lipid bilayers: Insights from multiscale molecular dynamics simulations.
    Biochim Biophys Acta 2015 May 16;1850(5):1017-25. Epub 2014 Sep 16.
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address:
    Background: The epidermal growth factor receptor (EGFR) is the best characterised member of the receptor tyrosine kinases, which play an important role in signalling across mammalian cell membranes. The EGFR juxtamembrane (JM) domain is involved in the mechanism of activation of the receptor, interacting with the anionic lipid phosphatidylinositol 4,5-bisphosphate (PIP2) in the intracellular leaflet of the cell membrane.

    Methods: Multiscale MD simulations were used to characterize PIP2-JM interactions. Read More
    Molecular dynamics study of a gelsolin-derived peptide binding to a lipid bilayer containing phosphatidylinositol 4,5-bisphosphate.
    Biopolymers 2003 ;71(1):49-70
    Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV1006, Latvia.
    Gelsolin is an actin-severing protein whose action is initiated by Ca(2+) and inhibited by binding to phosphorylated inositol lipid or phosphoinositides. The regions of gelsolin responsible for phosphoinositide binding are comprised of residues 150-169 (G150-169) and 135-142 (G135-142). The corresponding peptides possess similar binding potency as native gelsolin. Read More
    High concentrations of phosphatidylinositol-4,5-bisphosphate may promote actin filament growth by three potential mechanisms: inhibiting capping by neutrophil lysates, severing actin filaments and removing capping protein-beta2 from barbed ends.
    Biochim Biophys Acta 1997 Oct;1358(3):261-78
    Department of Medicine, Cooper Hospital / University Medical Center, UMDNJ / Robert Wood Johnson Medical School, Camden, NJ, USA.
    Cell locomotion requires rapid growth of cortical actin filaments whose barbed ends are capped in the resting cell. Phosphatidylinositol-4,5-bisphosphate (PIP2) may play a critical role as an intracellular messenger in cytoskeletal rearrangement after stimulation. We have examined the effects of PIP2 micelles on the Ca2+-independent actin filament capping activity in high speed supernatants of neutrophil lysates which we had previously demonstrated to be almost entirely due to capping protein-beta2, a homologue of cap Z. Read More
    Membrane targeting of the yeast exocyst complex.
    Biochim Biophys Acta 2015 Jul 30;1848(7):1481-9. Epub 2015 Mar 30.
    Institute of Experimental Botany, Academy of Sciences of the Czech Republic, 165 02 Prague, Czech Republic. Electronic address:
    The exocytosis is a process of fusion of secretory vesicles with plasma membrane, which plays a prominent role in many crucial cellular processes, e.g. secretion of neurotransmitters, cytokinesis or yeast budding. Read More