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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00475174" target="_blank" >RIV/61388963:_____/17:00475174 - isvavai.cz</a>

Alternative codes found

RIV/61389030:_____/17:00475201 RIV/61388955:_____/17:00475201

Result on the web

<a href="http://pubs.acs.org/doi/full/10.1021/jacs.6b11760" target="_blank" >http://pubs.acs.org/doi/full/10.1021/jacs.6b11760</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jacs.6b11760" target="_blank" >10.1021/jacs.6b11760</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of the American Chemical Society

ISSN

0002-7863

e-ISSN

—

Volume of the periodical

139

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

6

Pages from-to

4019-4024

UT code for WoS article

000397477700019

EID of the result in the Scopus database

2-s2.0-85016148911