The Conformation of Calreticulin Is Influenced by the Endoplasmic Reticulum Luminal Environment

Corbett, Elaine F.; Michalak, Karolina M.; Oikawa, Kimio; Johnson, Steven; Campbell, Iain D.; Eggleton, Paul; Kay, Cyril M.; Michalak, Marek

doi:10.1016/s0021-9258(19)61495-x

Cited by 113 publications

(37 citation statements)

References 66 publications

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“…It is well proven elsewhere that the metal ions can alter the physical properties of proteins, namely thermal stability and conformational rigidity/flexibility [33,39,40]. It is reported that zinc ion, through binding, can decrease the thermal stability and rigidity of calreticulin, causing a structural rearrangement and intensifying the hydrophobic character of the protein and paving the way for more self-association [39].…”

Section: Discussionmentioning

confidence: 99%

An Analysis of Inhibition of the Severe Acute Respiratory Syndrome Coronavirus 2 RNA-dependent Rna Polymerase By Zinc Ion: an in silico Approach

et al. 2021

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Background: Coronavirus disease 2019 is caused by exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was reported that Zn2+ is an inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV). We hypothesize that the same applies to the newly discovered SARS-CoV-2. Material & methods: We compared the structure of RNA-dependent RNA polymerase between SARS-CoV and SARS-CoV-2. The RdRp’s binding to Zn2+ was studied by metal ion-binding site prediction and docking server. Results: Several regions containing key residues were detected. The functional aspartic acid residues RdRp, 618D, 760D and 761D were among the predicted Zn2+-binding residues. Conclusion: The most probable mechanism of inhibition of RdRp by Zn2+ is binding to the active aspartic acid triad while other binding sites can further destabilize the enzyme or interfere with the fidelity-check mechanism.

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Section: Discussionmentioning

confidence: 99%

An Analysis of Inhibition of the Severe Acute Respiratory Syndrome Coronavirus 2 RNA-dependent Rna Polymerase By Zinc Ion: an in silico Approach

et al. 2021

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“…Since the mechanism of chaperon-assisted protein folding in the ER is ATP dependent, [29][30][31] we next investigated whether glucose starvation per se triggered intracellular energy depletion in cells and what could the role of DEX be in this imbalance of energy metabolism. To this end, we monitored the intracellular ATP concentrations in cells cultured either in 25 or 5.5 mM glucose medium for 24, 48, and 72 h. In a parallel experiment, the intracellular levels of ATP was also followed up in cells cultured in 5.5 mM glucose medium treated with 0.1 mM DEX.…”

Section: Dex Increases the Intracellular Levels Of Atp Through Upregulation Of Mitochondrial Genesmentioning

confidence: 99%

The effect of dexamethasone on defective nephrin transport caused by ER stress: A potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases

Fujii

Khoshnoodi

Takenaka

et al. 2006

Kidney International

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The mechanism by which glucocorticoids govern antiproteinuric effect in nephrotic syndrome remains unknown. Present study examined the protective role of dexamethasone (DEX) in the intracellular trafficking of nephrin under endoplasmic reticulum (ER) stress. Human embryonic kidney-293 cell line expressing a full-length human nephrin was cultured in mediums containing 5.5 or 25 mM glucose with or without DEX. The result revealed that glucose starvation evoked a rapid ER stress leading to formation of underglycosylated nephrin that was remained in the ER as a complex with calreticulin/calnexin. DEX rescued this interfered trafficking through binding to its receptor and stimulating the mitochondrial transcripts and adenosine 5' triphosphate (ATP) production, leading to synthesis of fully glycosylated nephrin. These results suggest that ER-stress in podocytes may cause alteration of nephrin N-glycosylation, which may be an underlying factor in the pathomechanism of the proteinuria in nephrotic syndrome. DEX may restore this imbalance by stimulating expression of mitochondrial genes, resulted in the production of ATP that is essential factor for proper folding machinery aided by the ER chaperones.

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“…In our co‐IP experiment, there was more interaction between ZAAT and calreticulin through ERdj3 depletion. Calreticulin is an ER luminal chaperone that is involved with the folding of newly synthesized glycoproteins [Corbett et al, ]. Calreticulin, together with calnexin and ERp57, forms the calreticulin/calnexin cycle that efficiently suppresses the aggregation of glycosylated proteins within the ER [Michalak et al, ].…”

Section: Discussionmentioning

confidence: 99%

Erdj3 Has an Essential Role for Z Variant Alpha‐1‐Antitrypsin Degradation

Khodayari

Marek

et al. 2017

J of Cellular Biochemistry

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Alpha‐1‐antitrypsin deficiency (AATD) is an inherited disease characterized by emphysema and liver disease. AATD is most often caused by a single amino acid substitution at amino acid 342 in the mature protein, resulting in the Z mutation of the alpha‐1‐antitrypsin gene (ZAAT). This substitution is associated with misfolding and accumulation of ZAAT in the endoplasmic reticulum (ER) of hepatocytes and monocytes, causing a toxic gain of function. Retained ZAAT is eliminated by ER‐associated degradation and autophagy. We hypothesized that alpha‐1‐antitrypsin (AAT)‐interacting proteins play critical roles in quality control of human AAT. Using co‐immunoprecipitation, we identified ERdj3, an ER‐resident Hsp40 family member, as a part of the AAT trafficking network. Depleting ERdj3 increased the rate of ZAAT degradation in hepatocytes by redirecting ZAAT to the ER calreticulin‐EDEM1 pathway, followed by autophagosome formation. In the Huh7.5 cell line, ZAAT ER clearance resulted from enhancing ERdj3‐mediated ZAAT degradation by silencing ERdj3 while simultaneously enhancing autophagy. In this context, ERdj3 suppression may eliminate the toxic gain of function associated with polymerization of ZAAT, thus providing a potential new therapeutic approach to the treatment of AATD‐related liver disease. J. Cell. Biochem. 118: 3090–3101, 2017. © 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals Inc.

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The Conformation of Calreticulin Is Influenced by the Endoplasmic Reticulum Luminal Environment

Cited by 113 publications

References 66 publications

An Analysis of Inhibition of the Severe Acute Respiratory Syndrome Coronavirus 2 RNA-dependent Rna Polymerase By Zinc Ion: an in silico Approach

An Analysis of Inhibition of the Severe Acute Respiratory Syndrome Coronavirus 2 RNA-dependent Rna Polymerase By Zinc Ion: an in silico Approach

The effect of dexamethasone on defective nephrin transport caused by ER stress: A potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases

Erdj3 Has an Essential Role for Z Variant Alpha‐1‐Antitrypsin Degradation

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