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Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition
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SYSNO ASEP 0475174 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition Author(s) Bilkova, E. (DE)
Pleskot, Roman (UOCHB-X)
Rissanen, S. (FI)
Sun, S. (US)
Czogalla, A. (DE)
Cwiklik, Lukasz (UOCHB-X) RID, ORCID
Róg, T. (FI)
Vattulainen, I. (FI)
Cremer, P. S. (US)
Jungwirth, Pavel (UOCHB-X) RID, ORCID
Coskun, U. (DE)Source Title Journal of the American Chemical Society. - : American Chemical Society - ISSN 0002-7863
Roč. 139, č. 11 (2017), s. 4019-4024Number of pages 6 s. Language eng - English Country US - United States Keywords membrane ; calcium ions ; PIP2 ; molecular dynamics Subject RIV CF - Physical ; Theoretical Chemistry OECD category Physical chemistry R&D Projects GA16-01074S GA ČR - Czech Science Foundation (CSF) Institutional support UOCHB-X - RVO:61388963 UT WOS 000397477700019 EID SCOPUS 85016148911 DOI 10.1021/jacs.6b11760 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2018 Electronic address http://pubs.acs.org/doi/full/10.1021/jacs.6b11760
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