Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F17%3A43895721" target="_blank" >RIV/60076658:12310/17:43895721 - isvavai.cz</a>
Result on the web
<a href="http://stke.sciencemag.org/content/10/507/eaao0358" target="_blank" >http://stke.sciencemag.org/content/10/507/eaao0358</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1126/scisignal.aao0358" target="_blank" >10.1126/scisignal.aao0358</a>
Alternative languages
Result language
angličtina
Original language name
Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription
Original language description
The channel Orai1 requires Ca2+ store depletion in the endoplasmic reticulum and an interaction with the Ca2+ sensor STIM1 to mediate Ca2+ signaling. Alterations in Orai1-mediated Ca2+ influx have been linked to several pathological conditions including immunodeficiency, tubular myopathy, and cancer. We screened large-scale cancer genomics data sets for dysfunctional Orai1 mutants. Five of the identified Orai1 mutations resulted in constitutively active gating and transcriptional activation. Our analysis showed that certain Orai1 mutations were clustered in the transmembrane 2 helix surrounding the pore, which is a trigger site for Orai1 channel gating. Analysis of the constitutively open Orai1 mutant channels revealed two fundamental gates that enabled Ca2+ influx: Arginine side chainswere displaced so they no longer blocked the pore, and a chain of water molecules formed in the hydrophobic pore region. Together, these results enabled us to identify a cluster of Orai1 mutations that trigger Ca2+ permeation associated with gene transcription and provide a gating mechanism for Orai1.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LM2015055" target="_blank" >LM2015055: Center for Systems Biology</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
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
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Volume of the periodical
10
Issue of the periodical within the volume
507
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
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UT code for WoS article
000416543000004
EID of the result in the Scopus database
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