Search results for "Cyst"
showing 10 items of 1960 documents
Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers.
2009
Ligand-mediated dimerization has emerged as a universal mechanism of growth factor receptor activation. Recent structural studies have shown that neurotrophins interact with dimers of the p75 neurotrophin receptor (p75NTR), but the actual mechanism of receptor activation has remained elusive. Here we show that p75NTR forms disulphide-linked dimers independently of neurotrophin binding through the highly conserved Cys257 in its transmembrane domain. Mutation of Cys257 abolished neurotrophin-dependent receptor activity but did not affect downstream signaling by the p75NTR/NgR/Lingo-1 complex in response to MAG, indicating the existence of distinct, ligand-specific activation mechanisms for p7…
Conformational changes involved in thermal aggregation processes of bovine serum albumin
2003
We report a kinetic study on thermal aggregation process of the model protein bovine serum albumin (BSA) in low concentration regime. Aim of this study is to provide information on relationship between conformational changes and initial step of aggregation. The experimental approach is based on steady-state fluorescence spectra of the two tryptophans located in two different domains, in way to study conformational changes in the surrounding of these residues. We also follow emission spectra of Fluorescein-5-Maleimide dye bound to the single free cysteine of BSA. Complementary information on the extent of aggregation and on the structural changes is obtained by Rayleigh scattering and circul…
The protease domain of procollagen C-proteinase (BMP1) lacks substrate selectivity, which is conferred by non-proteolytic domains.
2007
Abstract Procollagen C-proteinase (PCP) removes the C-terminal pro-peptides of procollagens and also processes other matrix proteins. The major splice form of the PCP is termed BMP1 (bone morphogenetic protein 1). Active BMP1 is composed of an astacin-like protease domain, three CUB (complement, sea urchin Uegf, BMP1) domains and one EGF-like domain. Here we compare the recombinant human full-length BMP1 with its isolated proteolytic domain to further unravel the functional influence of the CUB and EGF domains. We show that the protease domain alone cleaves truncated procollagen VII within the short telopeptide region into fragments of similar size as the full-length enzyme does. However, u…
An overview on chemical structures as ΔF508-CFTR correctors
2019
Deletion of phenylalanine at position 508 (F508del) in the CFTR protein, is the most common mutation causing cystic fibrosis (CF). F508del causes misfolding and rapid degradation of CFTR protein a defect that can be targeted with pharmacological agents termed “correctors”. Correctors belong to various chemical classes but are generally small molecules based on nitrogen sulfur or oxygen heterocycles. The mechanism of action of correctors is generally unknown but there is experimental evidence that some of them can directly act on mutant CFTR improving folding and stability. Here we overview the characteristics of the various F508del correctors described so far to obtain indications on key ch…
Disulfide stress: a novel type of oxidative stress in acute pancreatitis.
2013
Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and γ-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis…
The production of 85 kDa N-terminal fragment of apolipoprotein B in mutant HepG2 cells generated by targeted modification of apoB gene occurs by ALLN…
2010
Abstract To study the mechanism of low levels of full length and truncated apoB in individuals heterozygous for apoB truncation, a non-sense mutation was introduced in one of the three alleles of apob gene of HepG2 cells by homologous recombination. Despite very low levels of apoB-82 (1–2%) in the media, a prominent N-terminal apoB protein of 85 kDa (apoB-15) was secreted that fractionated at d > 1.065 in density gradient ultracentrifugation. The mechanism of production of this short protein was studied by 35S-methionine pulse–chase experiment. Oleate prevented presecretory degradation of apoB-100 in the cell and resulted in increased secretion of newly synthesized apoB-100 with decreases i…
Dithiothreitol Treatment of Madin-Darby Canine Kidney Cells Reversibly Blocks Export from the Endoplasmic Reticulum but Does Not Affect Vectorial Tar…
1995
Addition of dithiothreitol (DTT) to the culture medium of Madin-Darby canine kidney (MDCK) cells blocks transport of newly synthesized gp80 (clusterin, apolipoprotein J), a soluble marker protein for apical exocytosis in this epithelial cell line. In cells treated with DTT during pulse labeling, gp80 is retained in the endoplasmic reticulum. After removal of the reducing agent, gp80 is posttranslationally oxidized and secreted at the apical surface of MDCK cell monolayers. This demonstrates that when folded and oxidized posttranslationally, gp80 can acquire a conformation that exhibits sorting signals for vectorial targeting. In the continuous presence of DTT, the transepithelial electrical…
Identification of disulphide bonds in the refolding of bovine pancreatic RNase A
1996
Background: Comprehension of the rules that govern the folding process is still far from satisfactory, though it is nevertheless clear that all the information required to define the folding is encoded in the amino acid sequence. In proteins that contain disulphide bonds, folding is associated with disulphide bond formation. Protein species with different numbers of disulphides tend to accumulate during the process; these species can be trapped in a stable form, by quenching any remaining free SH groups, and then characterized in order to identify the disulphide bonds formed. Results The refolding pathway of reduced and denatured RNase A has been studied using mass spectrometric strategies …
The cytosolic Arabidopsis thaliana cysteine desulfurase ABA3 delivers sulfur to the sulfurtransferase STR18
2020
ABSTRACTThe biosynthesis of many sulfur-containing molecules depends on cysteine as a sulfur source. Cysteine desulfurase (CD) and rhodanese (Rhd) domain-containing protein families participate in the trafficking of sulfur for various metabolic pathways in bacteria and human, but their connection is not yet described in plants. The existence of natural chimeric proteins, however, containing both CD and Rhd domains in specific bacterial genera suggests a general interaction between both proteins. We report here the biochemical relationships between two cytosolic proteins from Arabidopsis thaliana, a Rhd domain containing protein, the sulfurtransferase 18 (STR18), and a CD isoform referred to…
Perturbed interactions of mutant proteolipid protein/DM20 with cholesterol and lipid rafts in oligodendroglia: implications for dysmyelination in spa…
2006
Missense mutations in the humanPLP1gene lead to dysmyelinating diseases with a broad range of clinical severity, ranging from severe Pelizaeus–Merzbacher disease (PMD) to milder spastic paraplegia type 2 (SPG-2). The molecular pathology has been generally attributed to endoplasmic reticulum (ER) retention of misfolded proteolipid protein (PLP) (and its splice isoform DM20) and induction of the unfolded protein response. As opposed to previous studies of heterologous expression systems, we have analyzed PLP/DM20 trafficking in oligodendroglial cells, thereby revealing differences between PMD and SPG-2-associated PLP/DM20 isoforms. PLPA242Vand DM20A242V(jimpy-msdin mice), associated with seve…