Affinage

SMDT1

Essential MCU regulator, mitochondrial · UniProt Q9H4I9

Length
107 aa
Mass
11.4 kDa
Annotated
2026-06-10
100 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMDT1 (EMRE) is a metazoan-specific, single-pass inner mitochondrial membrane protein that serves as an essential subunit of the mitochondrial calcium uniporter holocomplex, bridging the Ca2+-conducting MCU channel with the Ca2+-sensing regulators MICU1 and MICU2 (PMID:24231807). In its absence, uniporter channel activity is lost despite intact MCU expression and oligomerization, and the interaction of MCU with MICU1/MICU2 fails to form (PMID:24231807). EMRE adopts an Nin-Cout topology with its N-terminus in the matrix and C-terminus in the intermembrane space, and it contacts MCU on both sides of the membrane (PMID:27001609). Mechanistically, EMRE drives MCU channel opening through its transmembrane helix, which stabilizes the MCU "EMRE dependence domain" and the open conformation, while an N-terminal PKP motif strengthens MCU binding (PMID:33296646, PMID:32769116); a cryo-EM structure places EMRE at the periphery of the tetrameric transmembrane domain in contact with the first MCU helix, with Ca2+ conduction additionally requiring cardiolipin (PMID:32841658). EMRE also acts as a matrix Ca2+ sensor: its matrix-localized acidic C-terminus confers matrix Ca2+ inhibition of MCU, and removing or neutralizing it produces constitutive channel activation and Ca2+ overload, coupling Ca2+ sensors on both faces of the inner membrane (PMID:26774479). The MCU:EMRE assembly is variable, with most endogenous tetramers binding one or two EMRE subunits and stoichiometry differing across tissues, which tunes the cytoplasmic Ca2+ threshold for channel gating (PMID:32315830, PMID:35060355). In vivo, EMRE is required for rapid mitochondrial Ca2+ uptake (PMID:32017711), and cardiac-specific deletion abolishes uptake while attenuating Ca2+-stimulated ATP production, mPTP opening, the adrenergic response, and ischemia/reperfusion outcomes in a time-dependent manner (PMID:37230379). Loss-of-function SMDT1 variants in patients abolish EMRE protein and impair mitochondrial Ca2+ uptake, establishing a human disease link to defective uniporter function (PMID:37454773).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2013 High

    It was unknown how the calcium-sensing MICU proteins coupled to the calcium-conducting MCU; EMRE was identified as the missing essential subunit that bridges them and is required for uniporter channel activity.

    Evidence Quantitative MS of affinity-purified uniplex with siRNA knockdown, Co-IP, and electrophysiology

    PMID:24231807

    Open questions at the time
    • Topology and which membrane faces EMRE contacts MCU not yet defined
    • Structural basis of the bridging interaction unknown
    • No in vivo confirmation at this stage
  2. 2016 Medium

    The membrane orientation of EMRE and the side(s) on which it engages MCU were unresolved; a yeast reconstitution established Nin-Cout topology and showed EMRE contacts MCU on both membrane faces and is required for Ca2+ uptake rather than acting as a stabilizing chaperone.

    Evidence Yeast reconstitution with protease-protection topology assays, Ca2+ uptake, and Co-IP

    PMID:27001609

    Open questions at the time
    • Reconstitution in heterologous yeast system may not fully recapitulate mammalian complex
    • Atomic-level contact sites not mapped
  3. 2016 High

    Whether EMRE only enables channel opening or also restrains it was open; mutagenesis of its matrix acidic C-terminus showed this tail senses matrix Ca2+ and confers inhibitory gatekeeping requiring MICU1/MICU2 and cytoplasmic Ca2+.

    Evidence Mitoplast patch-clamp with C-terminal deletion and charge-neutralization mutants and Ca2+ uptake assays

    PMID:26774479

    Open questions at the time
    • Structural mechanism by which the acidic tail transmits inhibition not resolved
    • Quantitative Ca2+ affinity of the matrix sensor not defined
  4. 2019 Low

    Whether EMRE levels influence cell-death decisions was untested; overexpression in PDAC cells linked EMRE to pro-apoptotic signaling and mitochondrial fragmentation.

    Evidence SMDT1 overexpression with Western blotting of apoptosis markers and mitochondrial morphology analysis

    PMID:30782485

    Open questions at the time
    • Overexpression phenotype without loss-of-function validation of the EMRE-Drp1 link
    • Direct molecular connection between EMRE and Drp1/Fis1 phosphorylation not established
    • Not shown to depend on uniporter Ca2+ flux
  5. 2020 High

    How EMRE mechanically opens MCU was unknown; mutagenesis and chimera/crosslinking work showed the EMRE transmembrane helix stabilizes the MCU open state via a discrete EMRE-dependence domain, while the N-terminal PKP motif strengthens binding.

    Evidence Transmembrane and PKP mutagenesis, chimeric MCU constructs, crosslinking, electrophysiology, and Ca2+ uptake assays

    PMID:32769116 PMID:33296646

    Open questions at the time
    • Dynamic conformational transition captured only indirectly
    • How the gating signal couples to matrix C-terminal sensing not integrated
  6. 2020 High

    The structural placement of EMRE within the channel and its lipid requirements were undefined; a cryo-EM structure positioned EMRE at the periphery contacting the first MCU helix and reconstitution showed Ca2+ conduction requires cardiolipin.

    Evidence Cryo-EM of the Tribolium MCU-EMRE complex at 3.5 Å with proteoliposome reconstitution and Ca2+ uptake assays

    PMID:32841658

    Open questions at the time
    • Structure from insect ortholog; human-specific features not directly resolved
    • MICU1/MICU2-bound state not captured
    • Role of cardiolipin in gating versus assembly not separated
  7. 2020 Medium

    Whether EMRE stoichiometry shapes channel behavior was unknown; defined concatemer ratios showed 2EMRE:4MCU recapitulates endogenous gatekeeping and that EMRE abundance sets the cytoplasmic Ca2+ activation threshold.

    Evidence MCU-EMRE concatemers at fixed ratios with mitoplast electrophysiology and Ca2+ uptake assays

    PMID:32315830

    Open questions at the time
    • Single-lab concatemer constructs may not reflect native assembly dynamics
    • How cells regulate EMRE stoichiometry not addressed
  8. 2020 High

    Whether EMRE is required for uniporter function in a whole organism was untested; germline knockout mice lost rapid mitochondrial Ca2+ uptake, confirming the in vivo requirement.

    Evidence Germline EMRE knockout mouse with Ca2+ uptake in isolated mitochondria and metabolic phenotyping

    PMID:32017711

    Open questions at the time
    • Tissue-specific consequences not dissected by germline deletion
    • Disease-modification outcome in dystrophy model not fully resolved
  9. 2022 Medium

    Whether the in vitro variable stoichiometry occurs natively was open; quantitative tissue measurements showed EMRE is substoichiometric to MCU with tissue-specific MCU:EMRE ratios.

    Evidence Calibrated quantitative Western blotting of mouse tissue mitochondrial fractions with stoichiometric modeling

    PMID:35060355

    Open questions at the time
    • Functional consequence of tissue-specific ratios not directly measured
    • Estimates derived from statistical modeling rather than direct counting
  10. 2023 Medium

    Whether SMDT1 loss causes human disease was unknown; patient variants abolished EMRE protein and impaired mitochondrial Ca2+ uptake, with complementation confirming loss of function.

    Evidence Patient fibroblast analysis, complementation, Ca2+ uptake, OXPHOS activity, and morphology assays

    PMID:37454773

    Open questions at the time
    • Only two patients characterized
    • Clinical phenotype-genotype relationship not broadly defined
    • OXPHOS and morphology unaffected, leaving the cellular pathology mechanism open
  11. 2023 High

    The physiological role of EMRE-dependent Ca2+ uptake in the heart and its therapeutic relevance were unclear; inducible cardiac deletion linked EMRE loss to reduced Ca2+-stimulated ATP, attenuated mPTP and adrenergic responses, and time-dependent effects on ischemia/reperfusion injury.

    Evidence Tamoxifen-inducible cardiac-specific EMRE knockout with Ca2+ uptake, ATP, mPTP, adrenergic, and ex vivo I/R assays at two time points

    PMID:37230379

    Open questions at the time
    • Molecular basis of the long-term adaptive loss of I/R protection not defined
    • Translation to in vivo I/R and other tissues not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EMRE expression and stoichiometry are dynamically regulated to tune uniporter activity across tissues and physiological states, and how its dual matrix-sensing and gating functions are mechanistically coupled, remain open.
  • No mechanism for transcriptional or post-translational control of EMRE levels established
  • Integration of matrix C-terminal sensing with transmembrane gating not structurally resolved
  • Human disease spectrum from SMDT1 variants poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 1 GO:0140299 molecular sensor activity 1
Localization
GO:0005739 mitochondrion 3
Partners
MCUMICU1MICU2
Complex memberships
mitochondrial calcium uniporter complex (uniplex)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 EMRE (SMDT1) was identified as an essential component of the mitochondrial calcium uniporter holocomplex (uniplex) via quantitative mass spectrometry of affinity-purified uniplex. EMRE is a 10-kDa, metazoan-specific, single-transmembrane domain protein. In its absence, uniporter channel activity was lost despite intact MCU expression and oligomerization. EMRE was required for the interaction of MCU with MICU1 and MICU2, bridging the calcium-sensing role of MICU1/MICU2 with the calcium-conducting role of MCU. Quantitative mass spectrometry of affinity-purified complex, loss-of-function (siRNA knockdown), co-immunoprecipitation, electrophysiology Science High 24231807
2016 EMRE acts as a matrix Ca2+ sensor that governs gatekeeping of the mitochondrial Ca2+ uniporter. Deletion or charge neutralization of EMRE's matrix-localized acidic C terminus abolished matrix Ca2+ inhibition of MCU Ca2+ currents, resulting in MCU channel activation, enhanced mitochondrial Ca2+ uptake, and constitutively elevated matrix Ca2+ concentration. EMRE-dependent regulation requires IMS-localized MICU1 and MICU2 and cytoplasmic Ca2+, coupling Ca2+ sensors on both sides of the inner mitochondrial membrane. Patch-clamp electrophysiology of mitoplasts, EMRE deletion and charge-neutralization mutagenesis, mitochondrial Ca2+ uptake assays Cell Reports High 26774479
2016 EMRE topology was experimentally determined using a yeast expression system: its N-terminus projects into the mitochondrial matrix and its C-terminus projects into the intermembrane space. EMRE closely interacts with MCU on both sides of the inner membrane, and this interaction is essential for Ca2+ uptake. Co-expression of MCU with EMRE was necessary for Ca2+ uptake; EMRE expression alone was insufficient. EMRE was not a protein-stabilizing factor for other MCU complex subunits. Yeast expression system reconstitution, protease protection/topology assays, Ca2+ uptake assays, co-immunoprecipitation Biochimica et Biophysica Acta Medium 27001609
2020 EMRE deletion in a mouse model confirmed that EMRE is required for mitochondrial calcium uniporter function in vivo. EMRE-/- mice showed loss of rapid mitochondrial Ca2+ uptake. EMRE deletion in a muscular dystrophy model associated with mitochondrial Ca2+ overload was examined for disease modification. Germline EMRE knockout mouse model, mitochondrial Ca2+ uptake assays in isolated mitochondria, exercise and metabolic phenotyping JCI Insight High 32017711
2020 EMRE controls MCU activity via its transmembrane helix, while an N-terminal PKP motif strengthens binding with MCU. Opening of MCU requires hydrophobic interactions mediated by MCU residues near the pore's luminal end. A single mutation in human MCU that enhances these hydrophobic interactions allows Ca2+ transport without EMRE. EMRE facilitates MCU opening by stabilizing the open state in a conserved MCU gating mechanism. Mutagenesis of EMRE transmembrane domain and PKP motif, Ca2+ uptake assays, patch-clamp electrophysiology, chimeric MCU constructs Cell Reports High 33296646
2020 Variable assembly of EMRE and MCU creates functional channels with distinct gatekeeping profiles. Most endogenous channels contain two EMRE subunits per MCU tetramer. MCU-EMRE concatemers enforcing 1EMRE:4MCU restored Ca2+ uptake but not full gatekeeping; 4EMRE:4MCU enhanced gatekeeping; 2EMRE:4MCU recapitulated endogenous channel activity and gatekeeping. Increasing EMRE expression raises the cytoplasmic Ca2+ threshold for channel activation. MCU-EMRE concatemer expression, electrophysiology of mitoplasts, mitochondrial Ca2+ uptake assays, tagged subunit co-expression at defined ratios iScience Medium 32315830
2020 A cryo-EM structure of the MCU-EMRE complex from Tribolium castaneum at 3.5 Å resolution showed EMRE located at the periphery of the transmembrane domain, associating primarily with the first transmembrane helix of MCU in a tetrameric channel. Ca2+ uptake into proteoliposomes reconstituted with the purified MCU-EMRE complex was EMRE-dependent and also required the mitochondrial lipid cardiolipin. Cryo-EM structure determination, functional reconstitution in proteoliposomes, Ca2+ uptake assays Journal of Molecular Biology High 32841658
2020 Using chimeric proteins between EMRE-independent Dictyostelium discoideum MCU and human MCU, a 10-amino acid region in human MCU (the EMRE dependence domain, EDD) was identified as necessary for EMRE dependence. Crosslinking experiments showed EMRE directly interacts with human MCU at its transmembrane domains as well as the EDD. EMRE stabilizes the EDD of MCU, permitting channel opening and Ca2+ conductance. Chimeric MCU constructs, crosslinking experiments, Ca2+ uptake assays in cells lacking endogenous MCU/EMRE Life Science Alliance Medium 32769116
2019 SMDT1 (EMRE) overexpression in PDAC cells led to increased accumulation of pro-apoptotic protein BAX, decrease in anti-apoptotic proteins Bcl-2 and Bcl-xL, and more cytochrome c release. Mechanistically, SMDT1 overexpression promoted mitochondrial fragmentation by increasing phosphorylation of Drp1 and Fis1 while decreasing MFN1, and increased translocation of Drp1 from cytoplasm to mitochondria. SMDT1 overexpression, Western blotting for apoptosis markers, mitochondrial morphology analysis, cell viability/apoptosis assays Biochemical and Biophysical Research Communications Low 30782485
2023 Two patients with SMDT1 variants were characterized showing absence of EMRE protein, induction of MCU subcomplex formation (without EMRE), and impaired mitochondrial Ca2+ uptake in patient fibroblasts. Complementation experiments demonstrated that the SMDT1 variants caused loss of EMRE function. Oxidative phosphorylation enzyme activities, mitochondrial morphology, membrane potential, and routine respiration were not affected. Patient fibroblast analysis, complementation experiments, mitochondrial Ca2+ uptake assays, OXPHOS enzyme activity assays, mitochondrial morphology imaging Biochimica et Biophysica Acta - Molecular Basis of Disease Medium 37454773
2022 Quantitative analysis of MCU and EMRE in mouse tissue mitochondria showed that EMRE molecules are fewer than MCU molecules, with MCU:EMRE ratios significantly different among tissues. Statistical modeling suggested most endogenous MCU tetramers in brain bind 2 EMREs; in liver, kidney, and heart predominantly 1 EMRE; with nearly half of MCU tetramers in kidney and heart binding no EMRE, supporting variable stoichiometry of the MCU-EMRE complex in vivo. Quantitative Western blotting with characterized antibodies and standard proteins, stoichiometric calculations from mouse tissue mitochondrial fractions FEBS Open Bio Medium 35060355
2023 Cardiac-specific, tamoxifen-inducible EMRE deletion established that short-term EMRE loss abolished mitochondrial Ca2+ uptake, lowered basal mitochondrial Ca2+ levels, attenuated Ca2+-induced ATP production and mPTP opening, blunted cardiac adrenergic response, and improved maintenance of cardiac function in ex vivo ischemia/reperfusion. Long-term EMRE deletion similarly impaired mitochondrial Ca2+ handling but lost the protection from I/R injury, demonstrating time-dependent adaptive consequences. Conditional cardiac-specific tamoxifen-inducible EMRE knockout mouse, mitochondrial Ca2+ uptake assays, ATP production assays, mPTP opening assays, adrenergic stimulation, ex vivo I/R model Journal of Molecular and Cellular Cardiology High 37230379

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 EMRE is an essential component of the mitochondrial calcium uniporter complex. Science (New York, N.Y.) 558 24231807
1995 EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic cations and H+ and is soluble in organic solvents. The Journal of biological chemistry 261 7896833
2007 X-ray structure of EmrE supports dual topology model. Proceedings of the National Academy of Sciences of the United States of America 222 18024586
2000 A membrane-embedded glutamate is required for ligand binding to the multidrug transporter EmrE. The EMBO journal 171 10637227
2009 EmrE, a model for studying evolution and mechanism of ion-coupled transporters. Biochimica et biophysica acta 131 19167526
2016 EMRE Is a Matrix Ca(2+) Sensor that Governs Gatekeeping of the Mitochondrial Ca(2+) Uniporter. Cell reports 128 26774479
2000 An essential glutamyl residue in EmrE, a multidrug antiporter from Escherichia coli. The Journal of biological chemistry 123 10681497
2004 In vitro synthesis of fully functional EmrE, a multidrug transporter, and study of its oligomeric state. Proceedings of the National Academy of Sciences of the United States of America 114 14755055
2015 Tolerance of Listeria monocytogenes to Quaternary Ammonium Sanitizers Is Mediated by a Novel Efflux Pump Encoded by emrE. Applied and environmental microbiology 110 26590290
2003 Contributions of MexAB-OprM and an EmrE homolog to intrinsic resistance of Pseudomonas aeruginosa to aminoglycosides and dyes. Antimicrobial agents and chemotherapy 100 12499164
1996 Negative dominance studies demonstrate the oligomeric structure of EmrE, a multidrug antiporter from Escherichia coli. The Journal of biological chemistry 100 8940098
1999 Scanning cysteine accessibility of EmrE, an H+-coupled multidrug transporter from Escherichia coli, reveals a hydrophobic pathway for solutes. The Journal of biological chemistry 98 10383465
1996 Determining the secondary structure and orientation of EmrE, a multi-drug transporter, indicates a transmembrane four-helix bundle. Biochemistry 92 8679552
1998 NMR investigation of the multidrug transporter EmrE, an integral membrane protein. European journal of biochemistry 84 9688273
2004 The Escherichia coli multidrug transporter EmrE is a dimer in the detergent-solubilised state. Journal of molecular biology 83 15223321
2004 EmrE, a multidrug transporter from Escherichia coli, transports monovalent and divalent substrates with the same stoichiometry. The Journal of biological chemistry 79 15371426
2004 Structure of the multidrug resistance efflux transporter EmrE from Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 74 14970332
2003 Conformational changes in the multidrug transporter EmrE associated with substrate binding. Journal of molecular biology 68 12946360
2000 A common binding site for substrates and protons in EmrE, an ion-coupled multidrug transporter. FEBS letters 67 10878258
2005 RETRACTED: X-ray structure of the EmrE multidrug transporter in complex with a substrate. Science (New York, N.Y.) 66 16373573
2021 Structure and dynamics of the drug-bound bacterial transporter EmrE in lipid bilayers. Nature communications 58 33420032
2020 EMRE is essential for mitochondrial calcium uniporter activity in a mouse model. JCI insight 57 32017711
2001 In vitro monomer swapping in EmrE, a multidrug transporter from Escherichia coli, reveals that the oligomer is the functional unit. The Journal of biological chemistry 57 11572877
2013 Ligand-induced conformational changes of the multidrug resistance transporter EmrE probed by oriented solid-state NMR spectroscopy. Angewandte Chemie (International ed. in English) 56 23939862
2014 Intrinsic conformational plasticity of native EmrE provides a pathway for multidrug resistance. Journal of the American Chemical Society 54 24856154
2009 In vitro unfolding and refolding of the small multidrug transporter EmrE. Journal of molecular biology 53 19699749
2017 New free-exchange model of EmrE transport. Proceedings of the National Academy of Sciences of the United States of America 52 29114048
2016 Analysis of the structure and function of EMRE in a yeast expression system. Biochimica et biophysica acta 52 27001609
2001 A single carboxyl mutant of the multidrug transporter EmrE is fully functional. The Journal of biological chemistry 51 11278804
2005 Substrate-induced tryptophan fluorescence changes in EmrE, the smallest ion-coupled multidrug transporter. Biochemistry 49 15882076
2016 Protonation-dependent conformational dynamics of the multidrug transporter EmrE. Proceedings of the National Academy of Sciences of the United States of America 48 26787875
2004 The membrane topology of EmrE - a small multidrug transporter from Escherichia coli. FEBS letters 48 15044024
2010 Topologically random insertion of EmrE supports a pathway for evolution of inverted repeats in ion-coupled transporters. The Journal of biological chemistry 46 20308069
2014 Transported substrate determines exchange rate in the multidrug resistance transporter EmrE. The Journal of biological chemistry 45 24448799
2004 Investigation of ligand binding to the multidrug resistance protein EmrE by isothermal titration calorimetry. Biophysical journal 44 15501941
1997 EmrE, the smallest ion-coupled transporter, provides a unique paradigm for structure-function studies. The Journal of experimental biology 44 9050242
2012 Small multidrug resistance protein EmrE reduces host pH and osmotic tolerance to metabolic quaternary cation osmoprotectants. Journal of bacteriology 43 22942246
2007 The key residue for substrate transport (Glu14) in the EmrE dimer is asymmetric. The Journal of biological chemistry 43 18042544
2008 Identification of a glycine motif required for packing in EmrE, a multidrug transporter from Escherichia coli. The Journal of biological chemistry 40 18321856
2014 Outer membrane protein OmpW participates with small multidrug resistance protein member EmrE in quaternary cationic compound efflux. Journal of bacteriology 39 24633876
2008 Electron crystallography reveals plasticity within the drug binding site of the small multidrug transporter EmrE. Journal of molecular biology 39 18295794
2018 Structure of the EmrE multidrug transporter and its use for inhibitor peptide design. Proceedings of the National Academy of Sciences of the United States of America 37 30082384
2014 DddD is a CoA-transferase/lyase producing dimethyl sulfide in the marine environment. Biochemistry 37 25140443
2009 An emerging consensus for the structure of EmrE. Acta crystallographica. Section D, Biological crystallography 37 19171974
2007 Parallel topology of genetically fused EmrE homodimers. The EMBO journal 37 18059473
2004 The reconstitution and activity of the small multidrug transporter EmrE is modulated by non-bilayer lipid composition. Journal of molecular biology 37 15381431
2018 Electrostatic lock in the transport cycle of the multidrug resistance transporter EmrE. Proceedings of the National Academy of Sciences of the United States of America 35 30026196
2005 Exploring the binding domain of EmrE, the smallest multidrug transporter. The Journal of biological chemistry 35 16049002
2012 Antiparallel dimers of the small multidrug resistance protein EmrE are more stable than parallel dimers. The Journal of biological chemistry 33 22700980
2020 Mechanisms of EMRE-Dependent MCU Opening in the Mitochondrial Calcium Uniporter Complex. Cell reports 30 33296646
2022 High-pH structure of EmrE reveals the mechanism of proton-coupled substrate transport. Nature communications 28 35181664
2019 Identification of an Alternating-Access Dynamics Mutant of EmrE with Impaired Transport. Journal of molecular biology 27 31158365
2002 Optimization of expression and the purification by organic extraction of the integral membrane protein EmrE. Protein expression and purification 27 12356478
1996 Identification of residues in the translocation pathway of EmrE, a multidrug antiporter from Escherichia coli. The Journal of biological chemistry 27 8702890
2005 SMR proteins SugE and EmrE bind ligand with similar affinity and stoichiometry. Biochemical and biophysical research communications 26 16055085
2013 Combination of ¹⁵N reverse labeling and afterglow spectroscopy for assigning membrane protein spectra by magic-angle-spinning solid-state NMR: application to the multidrug resistance protein EmrE. Journal of biomolecular NMR 24 23539118
2020 Variable Assembly of EMRE and MCU Creates Functional Channels with Distinct Gatekeeping Profiles. iScience 23 32315830
2005 Organic solvent extracted EmrE solubilized in dodecyl maltoside is monomeric and binds drug ligand. Biochemical and biophysical research communications 23 15629134
2022 Crystal structures of bacterial small multidrug resistance transporter EmrE in complex with structurally diverse substrates. eLife 22 35254261
2016 Construction of an in Vitro Gene Screening System of the E. coli EmrE Transporter Using Liposome Display. Analytical chemistry 22 28193053
2022 Oceanospirillales containing the DMSP lyase DddD are key utilisers of carbon from DMSP in coastal seawater. Microbiome 21 35883169
2000 31P-CP-MAS NMR studies on TPP+ bound to the ion-coupled multidrug transport protein EmrE. FEBS letters 19 11034313
2019 SMDT1-driven change in mitochondrial dynamics mediate cell apoptosis in PDAC. Biochemical and biophysical research communications 18 30782485
2019 Inducing conformational preference of the membrane protein transporter EmrE through conservative mutations. eLife 18 31637997
2009 Multimeric forms of the small multidrug resistance protein EmrE in anionic detergent. Biochimica et biophysica acta 18 20036636
2008 Role of sequence bias in the topology of the multidrug transporter EmrE. Biochemistry 18 18616286
2014 A structured loop modulates coupling between the substrate-binding and dimerization domains in the multidrug resistance transporter EmrE. The Journal of biological chemistry 17 25406320
2005 A structure-based proposal for the catalytic mechanism of the bacterial acid phosphatase AphA belonging to the DDDD superfamily of phosphohydrolases. Journal of molecular biology 17 16330049
1999 EmrE, a small Escherichia coli multidrug transporter, protects Saccharomyces cerevisiae from toxins by sequestration in the vacuole. Journal of bacteriology 17 9922260
2023 Distinct effects of cardiac mitochondrial calcium uniporter inactivation via EMRE deletion in the short and long term. Journal of molecular and cellular cardiology 16 37230379
2020 Structure and Reconstitution of an MCU-EMRE Mitochondrial Ca2+ Uniporter Complex. Journal of molecular biology 16 32841658
2014 Blocking dynamics of the SMR transporter EmrE impairs efflux activity. Biophysical journal 16 25099800
2021 Asymmetric protonation of glutamate residues drives a preferred transport pathway in EmrE. Proceedings of the National Academy of Sciences of the United States of America 15 34607959
2013 Visualizing a multidrug resistance protein, EmrE, with major bacterial lipids using Brewster angle microscopy. Chemistry and physics of lipids 15 23384478
2011 Analyzing conformational changes in the transport cycle of EmrE. Current opinion in structural biology 15 22100111
2008 Novel monofunctional histidinol-phosphate phosphatase of the DDDD superfamily of phosphohydrolases. Journal of bacteriology 15 18223080
2003 Examination of EmrE conformational differences in various membrane mimetic environments. Biochemistry and cell biology = Biochimie et biologie cellulaire 15 12870870
2020 Evolutionary divergence reveals the molecular basis of EMRE dependence of the human MCU. Life science alliance 14 32769116
2013 In vivo trp scanning of the small multidrug resistance protein EmrE confirms 3D structure models'. Journal of molecular biology 14 23920359
2019 AAAA-DDDD Quadruple H-Bond-Assisted Ionic Interactions: Robust Bis(guanidinium)/Dicarboxylate Heteroduplexes in Water. Journal of the American Chemical Society 13 31789022
2000 Recursive use of evolutionary conservation data in molecular modeling of membrane proteins A model of the multidrug H+ antiporter emrE. European journal of biochemistry 13 10848957
2017 lncRNA C22orf32-1 contributes to the tumorigenesis of nasopharyngeal carcinoma. Oncology letters 12 28588717
2014 EmrE dimerization depends on membrane environment. Biochimica et biophysica acta 12 24680655
2014 Docking analysis insights quercetin can be a non-antibiotic adjuvant by inhibiting Mmr drug efflux pump in Mycobacterium sp. and its homologue EmrE in Escherichia coli. Journal of biomolecular structure & dynamics 12 25297690
2023 Microsecond Motion of the Bacterial Transporter EmrE in Lipid Bilayers. Journal of the American Chemical Society 11 37097985
2017 Structural and dynamic insights on the EmrE protein with TPP+ and related substrates through molecular dynamics simulations. Chemistry and physics of lipids 11 29288640
2002 Structural analysis of synthetic peptide fragments from EmrE, a multidrug resistance protein, in a membrane-mimetic environment. Biochemistry 11 12022866
2022 Small multidrug resistance protein EmrE phenotypically associates with OmpW, DcrB and YggM for osmotic stress protection by betaine in Escherichia coli. Microbiology (Reading, England) 9 36748554
2023 SMDT1 variants impair EMRE-mediated mitochondrial calcium uptake in patients with muscle involvement. Biochimica et biophysica acta. Molecular basis of disease 8 37454773
2023 Similar but different: Characterization of dddD gene-mediated DMSP metabolism among coral-associated Endozoicomonas. Science advances 8 37992165
2022 Quantitative analysis of mitochondrial calcium uniporter (MCU) and essential MCU regulator (EMRE) in mitochondria from mouse tissues and HeLa cells. FEBS open bio 8 35060355
2022 Cotranslational folding and assembly of the dimeric Escherichia coli inner membrane protein EmrE. Proceedings of the National Academy of Sciences of the United States of America 8 35994672
2017 BLaTM 2.0, a Genetic Tool Revealing Preferred Antiparallel Interaction of Transmembrane Helix 4 of the Dual-Topology Protein EmrE. Journal of molecular biology 8 28432015
2015 Structural and dynamic changes adopted by EmrE, multidrug transporter protein--Studies by molecular dynamics simulation. Biochimica et biophysica acta 8 26014489
2012 Spectroscopic analysis of small multidrug resistance protein EmrE in the presence of various quaternary cation compounds. Biochimica et biophysica acta 8 22326892
2015 Structural and functional comparison of hexahistidine tagged and untagged forms of small multidrug resistance protein, EmrE. Biochemistry and biophysics reports 7 29124131
2014 Functional response of the small multidrug resistance protein EmrE to mutations in transmembrane helix 2. FEBS letters 7 25157436
2008 Structural insights into the catalytic mechanism of the bacterial class B phosphatase AphA belonging to the DDDD superfamily of phosphohydrolases. Journal of molecular biology 5 18845157
2004 Crystallography of the integral membrane protein EmrE from Escherichia coli. Acta crystallographica. Section D, Biological crystallography 5 15583400
2024 Metadynamics Study of Lipid-Mediated Antibacterial Toxin Binding to the EmrE Multiefflux Protein. The journal of physical chemistry. B 4 39197021

Missed literature

Know a paper Affinage missed for SMDT1? Flag it for the maintainers and the community.

No submissions yet.