The plasma membrane protein Orai forms the pore of the calcium release-activated calcium (CRAC) channel and generates sustained cytosolic calcium signals when triggered by depletion of calcium from the endoplasmic reticulum. The crystal structure of Orai from Drosophila melanogaster, determined at 3.35 angstrom resolution, reveals that the calcium channel is composed of a hexameric assembly of Orai subunits arranged around a central ion pore. The pore traverses the membrane and extends into the cytosol. A ring of glutamate residues on its extracellular side forms the selectivity filter. A basic region near the intracellular side can bind anions that may stabilize the closed state. The architecture of the channel differs markedly from other ion channels and gives insight into the principles of selective calcium permeation and gating.
Improved methods for building protein models in electron density maps and the location of errors in these models
Membrane protein molecular weight determined by low-angle laser light-scattering photometry coupled with high-performance gel chromatography
Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores
Submicromolar La3+ concentrations block the calcium release-activated channel, and impair CD69 and CD25 expression in CD3- or thapsigargin-activated Jurkat cells
Conductance and permeation of monovalent cations through depletion-activated Ca2+ channels (ICRAC) in Jurkat T cells
Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution
Monovalent cation permeability and Ca(2+) block of the store-operated Ca(2+) current I(CRAC )in rat basophilic leukemia cells
Trimeric subunit stoichiometry of the glutamate transporters from Bacillus caldotenax and Bacillus stearothermophilus
STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane
Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins
Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity
Oligomeric states of proteins determined by size-exclusion chromatography coupled with light scattering, absorbance, and refractive index detectors
Regulation of CRAC channel activity by recruitment of silent channels to a high open-probability gating mode
Mapping the interacting domains of STIM1 and Orai1 in Ca2+ release-activated Ca2+ channel activation
Biochemical, pathological, and skeletal improvement of mucopolysaccharidosis VI after gene transfer to liver but not to muscle
Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation
A Cytosolic Homomerization and a Modulatory Domain within STIM1 C Terminus Determine Coupling to ORAI1 Channels
Increased hydrophobicity at the N terminus/membrane interface impairs gating of the severe combined immunodeficiency-related ORAI1 mutant
Molecular determinants of the coupling between STIM1 and Orai channels: differential activation of Orai1-3 channels by a STIM1 coiled-coil mutant
A single lysine in the N-terminal region of store-operated channels is critical for STIM1-mediated gating
Mutations in Orai1 transmembrane segment 1 cause STIM1-independent activation of Orai1 channels at glycine 98 and channel closure at arginine 91
The extended transmembrane Orai1 N-terminal (ETON) region combines binding interface and gate for Orai1 activation by STIM1.
Orai3 TM3 point mutation G158C alters kinetics of 2-APB-induced gating by disulfide bridge formation with TM2 C101
The contribution of Orai(CRACM)1 and Orai(CRACM)2 channels in store-operated Ca2+ entry and mediator release in human lung mast cells
Divergence of Ca(2+) selectivity and equilibrium Ca(2+) blockade in a Ca(2+) release-activated Ca(2+) channel
Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis
How ORAI and TRP channels interfere with each other: interaction models and examples from the immune system and the skin
Single-molecule analysis of diffusion and trapping of STIM1 and Orai1 at endoplasmic reticulum-plasma membrane junctions
Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg2+ channel MgtE
Differential roles of the C and N termini of Orai1 protein in interacting with stromal interaction molecule 1 (STIM1) for Ca2+ release-activated Ca2+ (CRAC) channel activation.
Activation of the endoplasmic reticulum calcium sensor STIM1 and store-operated calcium entry by rotavirus requires NSP4 viroporin activity
Non-NMDAR neuronal Ca(2+)-permeable channels in delayed neuronal death and as potential therapeutic targets for ischemic brain damage
Atomic force microscopy (AFM) imaging suggests that stromal interaction molecule 1 (STIM1) binds to Orai1 with sixfold symmetry
Glu106 targeted inhibitors of ORAI1 as potential Ca(2+) release-activated Ca(2+) (CRAC) channel blockers - molecular modeling and docking studies
The C- and N-terminal STIM1 binding sites on Orai1 are required for both trapping and gating CRAC channels
Genetically targeted single-channel optical recording reveals multiple Orai1 gating states and oscillations in calcium influx.
A calcium-accumulating region, CAR, in the channel Orai1 enhances Ca(2+) permeation and SOCE-induced gene transcription
Ca(2+) Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca(2+)-Dependent Nuclear Gene Expression
Phasing and structure of bestrophin-1: a case study in the use of heavy-atom cluster compounds with multi-subunit transmembrane proteins
Can I solve my structure by SAD phasing? Planning an experiment, scaling data and evaluating the useful anomalous correlation and anomalous signal
Identification of Orai1 channel inhibitors by using minimal functional domains to screen small molecule microarrays
Differential Redox Regulation of Ca²⁺ Signaling and Viability in Normal and Malignant Prostate Cells
Native STIM2 and ORAI1 proteins form a calcium-sensitive and thapsigargin-insensitive complex in cortical neurons
In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels -- mirage or pot of gold?
One ligand in dual roles: self-assembly of a bis-rhomboidal-shaped, three-dimensional molecular wheel
Identification of key amino acid residues responsible for internal and external pH sensitivity of Orai1/STIM1 channels
Combined immunodeficiency due to a homozygous mutation in ORAI1 that deletes the C-terminus that interacts with STIM 1
K(+) and Na(+) conduction in selective and nonselective ion channels via molecular dynamics simulations
The calcium feedback loop and T cell activation: how cytoskeleton networks control intracellular calcium flux
Multiple types of calcium channels arising from alternative translation initiation of the Orai1 message
Structural and stoichiometric determinants of Ca2+ release-activated Ca2+ (CRAC) channel Ca2+-dependent inactivation
Emerging roles of store-operated Ca²⁺ entry through STIM and ORAI proteins in immunity, hemostasis and cancer
The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy
Structural dynamics and topology of phosphorylated phospholamban homopentamer reveal its role in the regulation of calcium transport
Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing
Calcium, cancer and killing: the role of calcium in killing cancer cells by cytotoxic T lymphocytes and natural killer cells
Outstanding questions regarding the permeation, selectivity, and regulation of the mitochondrial calcium uniporter
Combined single channel and single molecule detection identifies subunit composition of STIM1-activated transient receptor potential canonical (TRPC) channels
Dominant mutations in ORAI1 cause tubular aggregate myopathy with hypocalcemia via constitutive activation of store-operated Ca²⁺ channels
The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface
Effects of electromagnetic field exposure on conduction and concentration of voltage gated calcium channels: A Brownian dynamics study
Visualizing Quantum Dot Labeled ORAI1 Proteins in Intact Cells Via Correlative Light and Electron Microscopy
Pathophysiological Significance of Store-Operated Calcium Entry in Megakaryocyte Function: Opening New Paths for Understanding the Role of Calcium in Thrombopoiesis
Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention
The stoichiometry of the TMEM16A ion channel determined in intact plasma membranes of COS-7 cells using liquid-phase electron microscopy
Calcium oscillations in fertilized pig oocytes are associated with repetitive interactions between STIM1 and ORAI1
Optimizing the fragment complementation of APEX2 for detection of specific protein-protein interactions in live cells
Orai1, 2, 3 and STIM1 promote store-operated calcium entry in pulmonary arterial smooth muscle cells
Mutant IP3 receptors attenuate store-operated Ca2+ entry by destabilizing STIM-Orai interactions in Drosophila neurons
Pore properties of Orai1 calcium channel dimers and their activation by the STIM1 ER calcium sensor.
ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain
A novel GABAA receptor ligand MIDD0301 with limited blood-brain barrier penetration relaxes airway smooth muscle ex vivo and in vivo
Generation and characterization of fully human monoclonal antibodies against human Orai1 for autoimmune disease
Stromal interaction molecule 1 (STIM1) and Orai1 mediate histamine-evoked calcium entry and nuclear factor of activated T-cells (NFAT) signaling in human umbilical vein endothelial cells.
Changes in Calcium Homeostasis and Gene Expression Implicated in Epilepsy in Hippocampi of Mice Overexpressing ORAI1
Tubular aggregate myopathy and Stormorken syndrome: Mutation spectrum and genotype/phenotype correlation.
A calcium/cAMP signaling loop at the ORAI1 mouth drives channel inactivation to shape NFAT induction
Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1
Physiological CRAC channel activation and pore properties require STIM1 binding to all six Orai1 subunits
STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology
Elevated Orai1 expression mediates tumor-promoting intracellular Ca2+ oscillations in human esophageal squamous cell carcinoma
Molecular mechanisms underlying inhibition of STIM1-Orai1-mediated Ca2+ entry induced by 2-aminoethoxydiphenyl borate
GABAA receptor α4 -subunit knockout enhances lung inflammation and airway reactivity in a murine asthma model
In vitro exposure to Hymenoptera venom and constituents activates discrete ionotropic pathways in mast cells
Identification of Key Pathways and Genes in the Orai2 Mediated Classical and Mesenchymal Subtype of Glioblastoma by Bioinformatic Analyses
Structural Mechanisms of Store-Operated and Mitochondrial Calcium Regulation: Initiation Points for Drug Discovery.
Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance
17β-Estradiol via Orai1 activates calcium mobilization to induce cell proliferation in epithelial ovarian cancer
Crystal structure of MICU2 and comparison with MICU1 reveal insights into the uniporter gating mechanism
The Number and Position of Orai3 Units within Heteromeric Store-Operated Ca2+ Channels Alter the Pharmacology of ICRAC
Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter
SOCE mediated by STIM and Orai is essential for pacemaker activity in the interstitial cells of Cajal in the gastrointestinal tract
The steroid hormone 20-hydroxyecdysone induces phosphorylation and aggregation of stromal interacting molecule 1 for store-operated calcium entry
Targeting Calcium Release-activated Calcium Channel Is Not Sufficient to Prevent Rejection in Nonhuman Primate Kidney Transplantation.
Cardiomyocyte-Specific Deletion of Orai1 Reveals Its Protective Role in Angiotensin-II-Induced Pathological Cardiac Remodeling.
A novel gain-of-function mutation in ORAI1 causes late-onset tubular aggregate myopathy and congenital miosis
Interplay between ER Ca2+ Binding Proteins, STIM1 and STIM2, Is Required for Store-Operated Ca2+ Entry
Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans
A temporal examination of calcium signaling in cancer- from tumorigenesis, to immune evasion, and metastasis
Furanocoumarins are a novel class of modulators for the transient receptor potential vanilloid type 1 (TRPV1) channel.
Ca2+ tunnelling through the ER lumen as a mechanism for delivering Ca2+ entering via store-operated Ca2+ channels to specific target sites
A coiled-coil clamp controls both conformation and clustering of stromal interaction molecule 1 (STIM1).
With the greatest care, stromal interaction molecule (STIM) proteins verify what skeletal muscle is doing
CRAC channel opening is determined by a series of Orai1 gating checkpoints in the transmembrane and cytosolic regions.
Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers.
Synthesis and Characterization of Store-Operated Calcium Entry Inhibitors Active in the Submicromolar Range.
Molecular Choreography and Structure of Ca2+ Release-Activated Ca2+ (CRAC) and KCa2+ Channels and Their Relevance in Disease with Special Focus on Cancer.
Gating and regulation of the calcium release-activated calcium channel: Recent progress from experiments and molecular modeling
More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.
Supra-Molecular Assemblies of ORAI1 at Rest Precede Local Accumulation into Puncta after Activation.
ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency
The rice TAL effector-dependent resistance protein XA10 triggers cell death and calcium depletion in the endoplasmic reticulum
Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.
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