scholarly journals Critical Role of Interdomain Interactions in the Conformational Change and Catalytic Mechanism of Endoplasmic Reticulum Aminopeptidase 1

Biochemistry ◽  
2017 ◽  
Vol 56 (10) ◽  
pp. 1546-1558 ◽  
Author(s):  
Athanasios Stamogiannos ◽  
Zachary Maben ◽  
Athanasios Papakyriakou ◽  
Anastasia Mpakali ◽  
Paraskevi Kokkala ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Conformational Change ◽  
Catalytic Mechanism ◽  
Critical Role ◽  
Endoplasmic Reticulum Aminopeptidase 1 ◽  
Interdomain Interactions

scholarly journals Critical Role of Endoplasmic Reticulum Aminopeptidase 1 in Determining the Length and Sequence of Peptides Bound and Presented by HLA-B27

2014 ◽  
Vol 66 (2) ◽  
pp. 284-294 ◽  
Author(s):  
Liye Chen ◽  
Roman Fischer ◽  
Yanchun Peng ◽  
Emma Reeves ◽  
Kirsty McHugh ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Critical Role ◽  
Hla B27 ◽  
Endoplasmic Reticulum Aminopeptidase 1

scholarly journals The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes

2020 ◽  
Vol 6 (51) ◽  
pp. eabc7209
Author(s):  
Meng Lu ◽  
Francesca W. van Tartwijk ◽  
Julie Qiaojin Lin ◽  
Wilco Nijenhuis ◽  
Pierre Parutto ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Nutritional Status ◽  
Neuronal Development ◽  
Critical Role ◽  
Causal Link ◽  
Global Distribution ◽  
Growth Defects ◽  
Cellular Environment ◽  
Axonal Extension

The endoplasmic reticulum (ER) comprises morphologically and functionally distinct domains: sheets and interconnected tubules. These domains undergo dynamic reshaping in response to changes in the cellular environment. However, the mechanisms behind this rapid remodeling are largely unknown. Here, we report that ER remodeling is actively driven by lysosomes, following lysosome repositioning in response to changes in nutritional status: The anchorage of lysosomes to ER growth tips is critical for ER tubule elongation and connection. We validate this causal link via the chemo- and optogenetically driven repositioning of lysosomes, which leads to both a redistribution of the ER tubules and a change of its global morphology. Therefore, lysosomes sense metabolic change in the cell and regulate ER tubule distribution accordingly. Dysfunction in this mechanism during axonal extension may lead to axonal growth defects. Our results demonstrate a critical role of lysosome-regulated ER dynamics and reshaping in nutrient responses and neuronal development.

scholarly journals SGTA-Dependent Regulation of Hsc70 Promotes Cytosol Entry of Simian Virus 40 from the Endoplasmic Reticulum

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Allison Dupzyk ◽  
Jeffrey M. Williams ◽  
Parikshit Bagchi ◽  
Takamasa Inoue ◽  
Billy Tsai
Keyword(s):  
Endoplasmic Reticulum ◽  
Biological Membrane ◽  
Critical Role ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Membrane Penetration ◽  
Critical Function ◽  
Nonenveloped Virus ◽  
Er Membrane

ABSTRACT Membrane penetration by nonenveloped viruses remains enigmatic. In the case of the nonenveloped polyomavirus simian virus 40 (SV40), the virus penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and then traffics to the nucleus to cause infection. We previously demonstrated that the cytosolic Hsc70-SGTA-Hsp105 complex is tethered to the ER membrane, where Hsp105 and SGTA facilitate the extraction of SV40 from the ER and transport of the virus into the cytosol. We now find that Hsc70 also ejects SV40 from the ER into the cytosol in a step regulated by SGTA. Although SGTA's N-terminal domain, which mediates homodimerization and recruits cellular adaptors, is dispensable during ER-to-cytosol transport of SV40, this domain appears to exert an unexpected post-ER membrane translocation function during SV40 entry. Our study thus establishes a critical function of Hsc70 within the Hsc70-SGTA-Hsp105 complex in promoting SV40 ER-to-cytosol membrane penetration and unveils a role of SGTA in controlling this step. IMPORTANCE How a nonenveloped virus transports across a biological membrane to cause infection remains mysterious. One enigmatic step is whether host cytosolic components are co-opted to transport the viral particle into the cytosol. During ER-to-cytosol membrane transport of the nonenveloped polyomavirus SV40, a decisive infection step, a cytosolic complex composed of Hsc70-SGTA-Hsp105 was previously shown to associate with the ER membrane. SGTA and Hsp105 have been shown to extract SV40 from the ER and transport the virus into the cytosol. We demonstrate here a critical role of Hsc70 in SV40 ER-to-cytosol penetration and reveal how SGTA controls Hsc70 to impact this process.

scholarly journals The role of tyrosine-9 and the C-terminal helix in the catalytic mechanism of Alpha-class glutathione S-transferases

1999 ◽  
Vol 343 (3) ◽  
pp. 525-531 ◽  
Author(s):  
Claire S. ALLARDYCE ◽  
Paul D. MCDONAGH ◽  
Lu-Yun LIAN ◽  
C. Roland WOLF ◽  
Gordon C. K. ROBERTS
Keyword(s):  
Conformational Change ◽  
Catalytic Mechanism ◽  
Ethacrynic Acid ◽  
Marked Decrease ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Turnover Number ◽  
Hydrophobic Substrate ◽  
Glutathione S Transferases

Glutathione S-transferases (GSTs) play a key role in the metabolism of drugs and xenobiotics. To investigate the catalytic mechanism, substrate binding and catalysis by the wild-type and two mutants of GST A1-1 have been studied. Substitution of the ‘essential’ Tyr9 by phenylalanine leads to a marked decrease in the kcat for 1-chloro-2,4-dinitrobenzene (CDNB), but has no affect on kcat for ethacrynic acid. Similarly, removal of the C-terminal helix by truncation of the enzyme at residue 209 leads to a decrease in kcat for CDNB, but an increase in kcat for ethacrynic acid. The binding of a GSH analogue increases the affinity of the wild-type enzyme for CDNB, and increases the rate of the enzyme-catalysed conjugation of this substrate with the small thiols 2-mercaptoethanol and dithiothreitol. This suggests that GSH binding produces a conformational change which is transmitted to the binding site for the hydrophobic substrate, where it alters both the affinity for the substrate and the catalytic-centre activity (‘turnover number‘) for conjugation, perhaps by increasing the proportion of the substrate bound productively. Neither of these two effects of GSH analogues are seen in the C-terminally truncated enzyme, indicating a role for the C-terminal helix in the GSH-induced conformational change.

scholarly journals Inhibition of Endoplasmic Reticulum Stress Reverses Synaptic Plasticity Deficits in Striatum of DYT1 Dystonia Mice

2021 ◽  
Author(s):  
Huaying Cai ◽  
Linhui Ni ◽  
Xingyue Hu ◽  
Xianjun Ding
Keyword(s):  
Endoplasmic Reticulum ◽  
Synaptic Plasticity ◽  
Er Stress ◽  
Critical Role ◽  
Stress Protein ◽  
Long Term Potentiation ◽  
Research Field ◽  
Protein Levels ◽  
Dyt1 Dystonia

Abstract Background & objectiveStriatal plasticity alterations caused by endoplasmic reticulum (ER) stress is supposed to be critically involved in the mechanism of DYT1 dystonia. In the current study, we expanded this research field by investigating the critical role of ER stress underlying synaptic plasticity impairment imposed by mutant heterozygous Tor1a+/- in a DYT1 dystonia mouse model.Methods & resultsLong-term depression (LTD) was failed to be induced, while long-term potentiation (LTP) was further strengthened in striatal spiny neurons (SPNs) from the Tor1a+/- DYT1 dystonia mice. Spine morphology analyses revealed a significant increase of both number of mushroom type spines and spine width in Tor1a+/- SPNs. In addition, increased AMPA receptor function and the reduction of NMDA/AMPA ratio in the postsynaptic of Tor1a+/- SPNs was observed, along with increased ER stress protein levels in Tor1a+/- striatum. Notably, ER stress inhibitors, tauroursodeoxycholic acid (TUDCA), could rescue LTD as well as AMPA currents.ConclusionThe current study illustrated the role of ER stress in mediating structural and functional plasticity alterations in Tor1a+/- SPNs. Inhibition of the ER stress by TUDCA is beneficial in reversing the deficits at the cellular and molecular levels. Remedy of dystonia associated neurological and motor functional impairment by ER stress inhibitors could be a recommendable therapeutic agent in clinical practice.

scholarly journals 0160 : Critical role of PTP1B in endoplasmic reticulum stress-induced endothelial dysfunction

2016 ◽  
Vol 8 (3) ◽  
pp. 250
Author(s):  
Pierre-Alain Thiébaut ◽  
Eugénie Delile ◽  
David Coquerel ◽  
Fabienne Tamion ◽  
Vincent Richard
Keyword(s):  
Endoplasmic Reticulum ◽  
Endothelial Dysfunction ◽  
Endoplasmic Reticulum Stress ◽  
Critical Role

scholarly journals The Chondroprotective Role of TMF in PGE2-Induced Apoptosis Associating with Endoplasmic Reticulum Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jianqiong Yang ◽  
Haiqing Liu ◽  
Linfu Li ◽  
Hai Liu ◽  
Weimei Shi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Critical Role ◽  
Osteoarthritic Chondrocytes ◽  
Induced Apoptosis

Endoplasmic reticulum stress (ERS) has been demonstrated to exhibit a critical role in osteoarthritic chondrocytes. Whether 5,7,3′,4′-tetramethoxyflavone (TMF) plays the chondroprotective role in inhibition of PGE2-induced chondrocytes apoptosis associating with ERS has not been reported. To investigate this, the activation of PERK, ATF6, and IRE1 signaling pathways in ERS in chondrocytes pretreated with PGE2was studied. By treatment with PGE2, the chondrocytes apoptosis was significantly increased, the proapoptotic CHOP and JNK were upregulated, the prosurvival GRP78 and XBP1 were downregulated, and GSK-3βwas also upregulated. However, TMF exhibited the effectively protective functions via counteracting these detrimental effects of PGE2. Finally, the inflammatory cytokine PGE2can activate ERS signaling and promote chondrocytes apoptosis, which might be associated with upregulation of GSK-3β. TMF exhibits a chondroprotective role in inhibiting PGE2-induced ERS and GSK-3β.

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