PuSH - Publication Server of Helmholtz Zentrum München

Bilkova, E. ; Pleskot, R.* ; Rissanen, S.* ; Sun, S.* ; Czogalla, A. ; Cwiklik, L.* ; Róg, T.* ; Vattulainen, I.* ; Cremer, P.S.* ; Jungwirth, P.* ; Coskun, Ü.

Calcium directly regulates phosphatidylinositol 4,5-Bbsphosphate headgroup conformation and recognition.

J. Am. Chem. Soc. 139, 4019-4024 (2017)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
Altmetric
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Molecular-dynamics Simulations; Pleckstrin Homology Domain; Local Ph Modulation; Intracellular Magnesium; Phospholipid-membranes; Cluster Formation; Lipid-bilayers; High-affinity; Air-water; Binding
ISSN (print) / ISBN 0002-7863
e-ISSN 1520-5126
Quellenangaben Volume: 139, Issue: 11, Pages: 4019-4024 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Publishing Place Washington
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)