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Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition

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    0475201 - ÚEB 2018 RIV US eng J - Journal Article
    Bilkova, E. - Pleskot, Roman - Rissanen, S. - Sun, S. - Czogalla, A. - Cwiklik, Lukasz - Róg, T. - Vattulainen, I. - Cremer, P. S. - Jungwirth, P. - Coskun, U.
    Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition.
    Journal of the American Chemical Society. Roč. 139, č. 11 (2017), s. 4019-4024. ISSN 0002-7863. E-ISSN 1520-5126
    R&D Projects: GA ČR GA13-19073S
    Institutional support: RVO:61389030 ; RVO:61388955
    Keywords : membrane * calcium ions * PIP2 * molecular dynamics
    Subject RIV: EB - Genetics ; Molecular Biology; CF - Physical ; Theoretical Chemistry (UFCH-W)
    OBOR OECD: Cell biology
    Impact factor: 14.357, year: 2017

    The orchestrated recognition of phosphoinositides and concomitant intracellular release of Ca2+ is pivotal to almost every aspect of cellular processes, including membrane homeostasis, cell division and growth, vesicle trafficking, as well as secretion. Although Ca2+ is known to directly impact phosphoinositide clustering, little is known about the molecular basis for this or its significance in cellular signaling. Here, we study the direct interaction of Ca2+ with phosphatidylinositol sphosphate (PI(4,5)P-2), the main lipid marker of the plasma membrane. Electrokinetic potential measurements of PI(4,5)P-2 containing liposomes reveal that Ca2+ as well as Mg2+ reduce the zeta potential of liposomes to nearly background levels of pure phosphatidylcholine membranes. Strikingly, lipid recognition by the default PI(4,5)P-2 lipid sensor, phospholipase C delta 1 pleckstrin homology domain (PLC delta 1-PH), is completely inhibited in the presence of Ca2+, while Mg2+ has no effect with 100 nm liposomes and modest effect with giant unilamellar vesicles. Consistent with biochemical data, vibrational sum frequency spectroscopy and atomistic molecular dynamics simulations reveal how Ca2+ binding to the PI(4,5)P-2 headgroup and carbonyl regions leads to confined lipid headgroup tilting and conformational rearrangements. We rationalize these findings by the ability of calcium to block a highly specific interaction between PLC delta 1-PH and PI(4,5)P-2, encoded within the conformational properties of the lipid itself. Our studies demonstrate the possibility that switchable phosphoinositide conformational states can serve as lipid recognition and controlled cell signaling mechanisms.
    Permanent Link: http://hdl.handle.net/11104/0272052
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