Aim: Human protein disulfide isomerase (hPDI) is a key enzyme and redox-regulated chaperone responsible for oxidative folding in the endoplasmic reticulum. This work aims to reveal molecular mechanism underlying functions of hPDI by determining crystal structures different redox states. Results: The (abb′xa′) both reduced oxidized states showed that four thioredoxin domains a, b, b′, a′ are arranged as horseshoe shape with two CGHC active sites, respectively, facing each other at ends. In...

Summary Metformin, an FDA ‐approved antidiabetic drug, has been shown to elongate lifespan in animal models. Nevertheless, the effects of metformin on human cells remain unclear. Here, we show that low‐dose treatment extends diploid fibroblasts and mesenchymal stem cells. We report a low dose upregulates endoplasmic reticulum‐localized glutathione peroxidase 7 ( GP x7). GP×7 expression levels are decreased senescent cells, x7 depletion results premature cellular senescence. also indicate...

Protein disulfide isomerase (PDI) catalyzes the formation of native disulfides peptide chains from either reduced form or randomly joined disulfides. So that thiols situated at distant parts polypeptide chain can be together to disulfides, has folded, least some extent, into conformation. It is suggested PDI promotes folding as well and plays a role similar chaperones in process. known multifunctional protein capable nonspecific binding. These properties are closely connected its possible...

Protein disulfide‐isomerase (PDI) in near stoichiometric concentrations promotes reactivation and prevents aggregation of guanidine‐hydrochloride‐denatured rhodanese during refolding upon dilution. PDI also suppresses thermal inactivation. The above‐mentioned properties displayed by completely satisfy the definition chaperone provide additional evidence to confirm hypothesis proposed previously [Wang, C. & Tsou, L. (1993) FASEB J. 7 , 1515–1517] that is both an enzyme a chaperone. Since...

Abstract Protein disulfide isomerase (PDI) is one of the most abundant and critical protein folding catalysts in endoplasmic reticulum eukaryotic cells. PDI consists four thioredoxin domains interacts with a wide range substrate partner proteins due to its intrinsic conformational flexibility. plays multifunctional roles variety pathophysiological events, both as an oxidoreductase molecular chaperone. Recent studies have revealed that conformation activity can be regulated multiple ways,...

Significance Fam20C is the bona fide “Golgi casein kinase” and generates majority of secreted phosphoproteome. Loss-of-function FAM20C mutations cause a type lethal osteosclerotic bone dysplasia called Raine syndrome. In this study, we find that resides in Golgi apparatus as transmembrane protein. Site-1 protease, key regulator cholesterol homeostasis, cleaves propeptide promotes its secretion activation. This proteolytic processing critical for osteoblast differentiation mineralization. Our...

Escherichia coli DnaJ, possessing both chaperone and thiol−disulfide oxidoreductase activities, is a homodimeric Hsp40 protein. Each subunit contains four copies of sequence -CXXCXGXG-, which coordinate with two Zn(II) ions to form an unusual topology C4-type zinc fingers, C144DVC147Zn(II)C197NKC200 (Zn1) C161PTC164Zn(II)C183PHC186 (Zn2). Studies on five DnaJ mutants Cys in Zn2 replaced by His or Ser (C183H, C186H, C161H/C183H, C164H/183H, C161S/C164S) reveal that substitutions one residues...

Abstract Disulfide bonds play essential roles in the folding of secretory and plasma membrane proteins endoplasmic reticulum (ER). In eukaryotes, protein disulfide isomerase (PDI) is an enzyme catalyzing bond formation isomerization substrates. The Arabidopsis (Arabidopsis thaliana) genome encodes diverse PDIs including structurally distinct subgroups PDI-L PDI-M/S. It remains unclear how these AtPDIs function to catalyze correct formation. We found that one ER oxidoreductin-1 (Ero1),...

DsbC, a member of the Dsb family in periplasm Gram-negative bacteria, is not only disulfide isomerase but also chaperone. Five DsbC mutants with Cys active site sequence Cys98-Gly-Tyr-Cys101 and nonactive Cys141-Cys163 replaced by Ser have been studied. The results show that residues are necessary for enzyme activities required chaperone activity, while lack decreased activity assisting reactivation denaturedd-glyceraldehyde-3-phosphate dehydrogenase has no effect on activities. Wild-type...

The folding/unfolding of a protein structure has been studied through measuring the donor–donor energy migration between two fluorescent probes (F) coupled selectively to N termini homodimeric DsbC (see picture). fluorometric strategy provides convenient and reliable method investigate conformational changes in dimeric proteins. Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460072_s.pdf or from author. Please note: publisher...

The thermal stability of DsbC, a homodimeric protein disulfide isomerase in prokaryotic periplasm, has been studied by using temperature-dependent Fourier transformation infrared and time-resolved spectroscopy coupled with temperature-jump initiation. absorbance titration curves for thermal-induced unfolding DsbC D2O exhibit three-state transition the first midpoint temperature at 37.1 ± 1.1°C corresponding to dissociation, second >74.5°C global aggregation. dissociation phosphate buffer...

Metabolic syndrome (MetS) is a major health issue worldwide accompanied by cardiovascular comorbidities. Growth differentiation factor-15 (GDF-15) stress-responsive cytokine expressed in cardiomyocytes, adipocytes, macrophages, and endothelial cells. Previous research elderly subjects revealed that GDF-15 levels were associated with the MetS. However, association between MetS or its components non-elderly remains unclear. In this study, total of 279 younger than 65-year-old (n = 84) without...

Like glutathione or dithiothreitol, metallothionein effects the formation of pancreatic ribonuclease A from its S‐sulfonated derivative catalyzed by protein disulfide isomerase. EDTA increases yield activity recovery with but does not affect reaction dithiothreitol. also reactivity thiol groups in 5,5′‐dithiobis‐(2‐nitrobenzoic acid) chelation zinc ions. It is suggested that form a part pool cellular thiols regulation redox reactions and their availability modulated chelation.

Upon dilution, d-glyceraldehyde-3-phosphate dehydrogenase (GADPH) that has been fully inactivated, but only partially unfolded, in dilute guanidine hydrochloride (GuHCl) recovers activity completely. The unfolded enzyme, however, is re-activated to a limited extent after and refolds rapidly burst phase folded intermediate characterized by increases both the emission intensity of intrinsic fluorescence binding 8-anilino-1-naphthalenesulphonic acid (ANS). This aggregates with time lag few...

Das Falten und Entfalten einer Proteinstruktur wurde anhand der Donor-Donor-Energiewanderung zwischen zwei Fluoreszenzsonden (F) untersucht, die selektiv an N-Termini des homodimeren DsbC-Proteins gekuppelt sind (siehe Bild). Die Fluorometrie-Strategie bietet eine bequeme verlässliche Methode, um Konformationsänderungen in dimeren Proteinen zu analysieren. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z460072_s.pdf or from...

Thermodynamics of the refolding denatured d ‐glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) assisted by protein disulfide isomerase (PDI), a molecular chaperone, has been studied isothermal microcalorimetry at different molar ratios PDI/GAPDH and temperatures using two thermodynamic models proposed for chaperone–substrate binding chaperone‐assisted substrate folding, respectively. The GAPDH folding intermediates to PDI is driven large favorable enthalpy decrease with unfavorable entropy...