Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Frischauf, I; Litviňuková, M; Schober, R; Zayats, V; Svobodová, B; Bonhenry, D; Lunz, V; Cappello, S; Tociu, L; Reha, D; Stallinger, A; Hochreiter, A; Pammer, T; Butorac, C; Muik, M; Groschner, K; Bogeski, I; Ettrich, RH; Romanin, C; Schindl, R.
Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription.
Sci Signal. 2017; 10(507): [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Groschner Klaus
Schindl Rainer
Svobodova Barbora

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Number of Figures: 9
| | | | | | | | |
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. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Arginine - metabolism
Calcium - metabolism
Cell Membrane - metabolism
Drosophila melanogaster -
Genomics -
HCT116 Cells -
HEK293 Cells -
Humans -
Ion Channel Gating - genetics
Molecular Dynamics Simulation -
Muscular Diseases - metabolism
Mutation -
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Neoplasms - metabolism
ORAI1 Protein - genetics
ORAI1 Protein - metabolism
Patch-Clamp Techniques -
Protein Structure, Secondary - genetics
Stromal Interaction Molecule 1 - genetics
Stromal Interaction Molecule 1 - metabolism
Transcriptional Activation - genetics

© Med Uni Graz Impressum