Sequential activation of STIM1 links Ca2+ with luminal domain unfolding
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F19%3A00520315" target="_blank" >RIV/61388971:_____/19:00520315 - isvavai.cz</a>
Result on the web
<a href="https://stke.sciencemag.org/content/12/608/eaax3194" target="_blank" >https://stke.sciencemag.org/content/12/608/eaax3194</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1126/scisignal.aax3194" target="_blank" >10.1126/scisignal.aax3194</a>
Alternative languages
Result language
angličtina
Original language name
Sequential activation of STIM1 links Ca2+ with luminal domain unfolding
Original language description
The stromal interaction molecule 1 (STIM1) has two important functions, Ca2+ sensing within the endoplasmic reticulum and activation of the store-operated Ca2+ channel Orai1, enabling plasma-membrane Ca2+ influx. We combined molecular dynamics (MD) simulations with live-cell recordings and determined the sequential Ca2+-dependent conformations of the luminal STIM1 domain upon activation. Furthermore, we identified the residues within the canonical and noncanonical EF-hand domains that can bind to multiple Ca2+ ions. In MD simulations, a single Ca 2+ ion was sufficient to stabilize the luminal STIM1 complex. Ca2+ store depletion destabilized the two EF hands, triggering disassembly of the hydrophobic cleft that they form together with the stable SAM domain. Point mutations associated with tubular aggregate myopathy or cancer that targeted the canonical EF hand, and the hydrophobic cleft yielded constitutively clustered STIM1, which was associated with activation of Ca2+ entry through Orai1 channels. On the basis of our results, we present a model of STIM1 Ca2+ binding and refine the currently known initial steps of STIM1 activation on a molecular level.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10610 - Biophysics
Result continuities
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)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Science Signaling
ISSN
1945-0877
e-ISSN
—
Volume of the periodical
12
Issue of the periodical within the volume
608
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
eaax3194
UT code for WoS article
000497952300002
EID of the result in the Scopus database
2-s2.0-85075325660