-
Je něco špatně v tomto záznamu ?
Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription
I. Frischauf, M. Litviňuková, R. Schober, V. Zayats, B. Svobodová, D. Bonhenry, V. Lunz, S. Cappello, L. Tociu, D. Reha, A. Stallinger, A. Hochreiter, T. Pammer, C. Butorac, M. Muik, K. Groschner, I. Bogeski, RH. Ettrich, C. Romanin, R. Schindl,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Perzistentní odkaz
https://www.medvik.cz/link/bmc18033510
- MeSH
- aktivace transkripce genetika MeSH
- arginin metabolismus MeSH
- buněčná membrána metabolismus MeSH
- Drosophila melanogaster MeSH
- gating iontového kanálu genetika MeSH
- genomika MeSH
- HCT116 buňky MeSH
- HEK293 buňky MeSH
- lidé MeSH
- metoda terčíkového zámku MeSH
- mutace MeSH
- nádorové proteiny genetika metabolismus MeSH
- nádory metabolismus MeSH
- nemoci svalů metabolismus MeSH
- protein ORAI1 genetika metabolismus MeSH
- protein STIM1 genetika metabolismus MeSH
- sekundární struktura proteinů genetika MeSH
- simulace molekulární dynamiky MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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 chains were 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.
Institute for Biophysics Medical University of Graz Graz A 8010 Austria
Institute for Molecular Biosciences Karl Franzens University Graz Graz A 8010 Austria
Institute of Biophysics JKU Life Science Center Johannes Kepler University Linz Linz A 4020 Austria
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc18033510
- 003
- CZ-PrNML
- 005
- 20181012095947.0
- 007
- ta
- 008
- 181008s2017 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1126/scisignal.aao0358 $2 doi
- 035 __
- $a (PubMed)29184031
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Frischauf, Irene $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria.
- 245 10
- $a Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription / $c I. Frischauf, M. Litviňuková, R. Schober, V. Zayats, B. Svobodová, D. Bonhenry, V. Lunz, S. Cappello, L. Tociu, D. Reha, A. Stallinger, A. Hochreiter, T. Pammer, C. Butorac, M. Muik, K. Groschner, I. Bogeski, RH. Ettrich, C. Romanin, R. Schindl,
- 520 9_
- $a 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 chains were 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.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a arginin $x metabolismus $7 D001120
- 650 _2
- $a vápník $x metabolismus $7 D002118
- 650 _2
- $a buněčná membrána $x metabolismus $7 D002462
- 650 _2
- $a Drosophila melanogaster $7 D004331
- 650 _2
- $a genomika $7 D023281
- 650 _2
- $a HCT116 buňky $7 D045325
- 650 _2
- $a HEK293 buňky $7 D057809
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a gating iontového kanálu $x genetika $7 D015640
- 650 _2
- $a simulace molekulární dynamiky $7 D056004
- 650 _2
- $a nemoci svalů $x metabolismus $7 D009135
- 650 _2
- $a mutace $7 D009154
- 650 _2
- $a nádorové proteiny $x genetika $x metabolismus $7 D009363
- 650 _2
- $a nádory $x metabolismus $7 D009369
- 650 _2
- $a protein ORAI1 $x genetika $x metabolismus $7 D000071740
- 650 _2
- $a metoda terčíkového zámku $7 D018408
- 650 _2
- $a sekundární struktura proteinů $x genetika $7 D017433
- 650 _2
- $a protein STIM1 $x genetika $x metabolismus $7 D000071737
- 650 _2
- $a aktivace transkripce $x genetika $7 D015533
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Litviňuková, Monika $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria. Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Cardiovascular and Metabolic Sciences, Berlin D-13125, Germany.
- 700 1_
- $a Schober, Romana $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria.
- 700 1_
- $a Zayats, Vasilina $u Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic. Center of New Technologies, University of Warsaw, Warsaw 02-097, Poland.
- 700 1_
- $a Svobodová, Barbora $u Institute for Biophysics, Medical University of Graz, Graz A-8010, Austria.
- 700 1_
- $a Bonhenry, Daniel $u Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic.
- 700 1_
- $a Lunz, Victoria $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria.
- 700 1_
- $a Cappello, Sabrina $u Molecular Physiology, Institute of Cardiovascular Physiology, University Medical Center, Georg August University Göttingen, Göttingen, Niedersachsen 37073, Germany. Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, Medical Faculty, Saarland University, Homburg D-66421, Germany.
- 700 1_
- $a Tociu, Laura $u Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic. University of Chicago, Chicago, IL 60637, USA.
- 700 1_
- $a Reha, David $u Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic. Faculty of Sciences, University of South Bohemia, Nové Hrady CZ-373 33, Czech Republic.
- 700 1_
- $a Stallinger, Amrutha $u Institute for Molecular Biosciences, Karl-Franzens-University Graz, Graz A-8010, Austria.
- 700 1_
- $a Hochreiter, Anna $u Institute for Experimental and Clinical Cell Therapy, Paracelsus Medical University, Salzburg A-5020, Austria.
- 700 1_
- $a Pammer, Teresa $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria.
- 700 1_
- $a Butorac, Carmen $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria.
- 700 1_
- $a Muik, Martin $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria.
- 700 1_
- $a Groschner, Klaus $u Institute for Biophysics, Medical University of Graz, Graz A-8010, Austria.
- 700 1_
- $a Bogeski, Ivan $u Molecular Physiology, Institute of Cardiovascular Physiology, University Medical Center, Georg August University Göttingen, Göttingen, Niedersachsen 37073, Germany.
- 700 1_
- $a Ettrich, Rüdiger H $u Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Nové Hrady CZ-373 33, Czech Republic. Faculty of Sciences, University of South Bohemia, Nové Hrady CZ-373 33, Czech Republic.
- 700 1_
- $a Romanin, Christoph $u Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz A-4020, Austria.
- 700 1_
- $a Schindl, Rainer $u Institute for Biophysics, Medical University of Graz, Graz A-8010, Austria. rainer.schindl@medunigraz.at.
- 773 0_
- $w MED00190083 $t Science signaling $x 1937-9145 $g Roč. 10, č. 507 (2017)
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/29184031 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20181008 $b ABA008
- 991 __
- $a 20181012100439 $b ABA008
- 999 __
- $a ok $b bmc $g 1340929 $s 1030504
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 10 $c 507 $e 20171128 $i 1937-9145 $m Science signaling $n Sci Signal $x MED00190083
- LZP __
- $a Pubmed-20181008
