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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Chem+Soc
2017 ; 139
(11
): 4019-4024
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Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup
Conformation and Recognition
#MMPMID28177616
Bilkova E
; Pleskot R
; Rissanen S
; Sun S
; Czogalla A
; Cwiklik L
; Róg T
; Vattulainen I
; Cremer PS
; Jungwirth P
; Coskun Ü
J Am Chem Soc
2017[Mar]; 139
(11
): 4019-4024
PMID28177616
show ga
The orchestrated recognition of phosphoinositides and concomitant intracellular
release of Ca(2+) is pivotal to almost every aspect of cellular processes,
including membrane homeostasis, cell division and growth, vesicle trafficking, as
well as secretion. Although Ca(2+) 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
Ca(2+) with phosphatidylinositol 4,5-bisphosphate (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 Ca(2+) as well as Mg(2+) 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
?1-PH), is completely inhibited in the presence of Ca(2+), while Mg(2+) 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 Ca(2+) 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 ?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.