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

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http://hdl.handle.net/10138/224435

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Bilkova , E , Pleskot , R , Rissanen , S , Sun , S , Czogalla , A , Cwiklik , L , Rog , T , Vattulainen , I , Cremer , P S , Jungwirth , P & Coskun , U 2017 , ' Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition ' , Journal of the American Chemical Society , vol. 139 , no. 11 , pp. 4019-4024 . https://doi.org/10.1021/jacs.6b11760

Title: Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition
Author: Bilkova, Eva; Pleskot, Roman; Rissanen, Sami; Sun, Simou; Czogalla, Aleksander; Cwiklik, Lukasz; Rog, Tomasz; Vattulainen, Ilpo; Cremer, Paul S.; Jungwirth, Pavel; Coskun, Uenal
Contributor: University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
Date: 2017-03-22
Language: eng
Number of pages: 6
Belongs to series: Journal of the American Chemical Society
ISSN: 0002-7863
URI: http://hdl.handle.net/10138/224435
Abstract: 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.
Subject: MOLECULAR-DYNAMICS SIMULATIONS
PLECKSTRIN HOMOLOGY DOMAIN
LOCAL PH MODULATION
INTRACELLULAR MAGNESIUM
PHOSPHOLIPID-MEMBRANES
CLUSTER FORMATION
LIPID-BILAYERS
HIGH-AFFINITY
AIR-WATER
BINDING
116 Chemical sciences
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