Search results for "protein aggregation"
showing 10 items of 128 documents
Hsp90 dictates viral sequence space by balancing the evolutionary tradeoffs between protein stability, aggregation and translation rate
2017
AbstractAcquisition of mutations is central to evolution but the detrimental effects of most mutations on protein folding and stability limit protein evolvability. Molecular chaperones, which suppress aggregation and facilitate polypeptide folding, are proposed to promote sequence diversification by buffering destabilizing mutations. However, whether and how chaperones directly control protein evolution remains poorly understood. Here, we examine the effect of reducing the activity of the key eukaryotic chaperone Hsp90 on poliovirus evolution. Contrary to predictions of a buffering model, inhibiting Hsp90 increases population sequence diversity and promotes accumulation of mutations reducin…
Assessment of temperature effects on beta-aggregation of native and glycated albumin by FTIR spectroscopy and PAGE: relations between structural chan…
2007
Abstract Structural modifications of bovine serum albumin (BSA) induced by heating, and the involvement of glycation of albumin in such processing were studied by using Fourier transform infrared spectroscopy (FTIR) and polyacrylamide gel electrophoresis (PAGE). For native BSA, heating treatments gave rise to β structures which were amplified to the detriment of α-helix form, and which were associated with increased aggregation. A very high correlation was obtained between FTIR Amide I band evolution and aggregation rate parameters, showing the contribution of β-form in aggregates formation. We further assessed the effect of glycation on protein sensibility to heating treatments. A reductio…
Deciphering metal-induced oxidative damages on glycated albumin structure and function
2014
Background: Metal ions such as copper or zinc are involved in the development of neurodegenerative pathologies and metabolic diseases such as diabetes mellitus. Albumin structure and functions are impaired following metal-and glucose-mediated oxidative alterations. The aim of this study was to elucidate effects of Cu(II) and Zn(II) ions on glucose-induced modifications in albumin by focusing on glycation, aggregation, oxidation and functional aspects. Methods: Aggregation and conformational changes in albumin were monitored by spectroscopy, fluorescence and microscopy techniques. Biochemical assays such as carbonyl, thiol groups, albumin-bound Cu, fructosamine and amine group measurements w…
Glycation alters ligand binding, enzymatic, and pharmacological properties of human albumin.
2015
Albumin, the major circulating protein in blood plasma, can be subjected to an increased level of glycation in a diabetic context. Albumin exerts crucial pharmacological activities through its drug binding capacity, i.e., ketoprofen, and via its esterase-like activity, allowing the conversion of prodrugs into active drugs. In this study, the impact of the glucose-mediated glycation on the pharmacological and biochemical properties of human albumin was investigated. Aggregation product levels and the redox state were quantified to assess the impact of glycation-mediated changes on the structural properties of albumin. Glucose-mediated changes in ketoprofen binding properties and esterase-lik…
Thermal aggregation of glycated bovine serum albumin
2010
International audience; Aggregation and glycation processes in proteins have a particular interest in medicine fields and in food technology. Serum albumins are model proteins which are able to self-assembly in aggregates and also sensitive to a non-enzymatic glycation in cases of diabetes. In this work, we firstly reported a study on the glycation and oxidation effects on the structure of bovine serum albumin (BSA). The experimental approach is based on the study of conformational changes of BSA at secondary and tertiary structures by FTIR absorption and fluorescence spectroscopy, respectively. Secondly, we analysed the thermal aggregation process on BSA glycated with different glucose con…
Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates.
2013
Summary Aggregation of misfolded proteins and the associated loss of neurons are considered a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, Creutzfeld-Jacob disease and Pick's disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognizes various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent m…
Immune Response to Tumor Stress Proteins—Implications for Vaccine Development Against Cancer
2000
Publisher Summary Stress proteins or heat shock proteins (HSP) belong to the most conserved proteins. The conservation of stress proteins stems from their basic and vital role in cells: Prevention of protein aggregation under stress and physiological conditions. Stress proteins are important target antigens in autoimmune diseases and during certain bacterial infections. This chapter reviews the immunogenicity of stress proteins of tumor cells, stimulation of T cell response by tumor stress proteins and implications this Tcell response have for immunity against the tumor or autoimmunity. The expression of stress proteins in cancer is altered. An overexpression of constitutively expressed or …
Self-Organization Pathways and Spatial Heterogeneity in Insulin Amyloid Fibril Formation
2009
At high temperature and low pH, the protein hormone insulin is highly prone to form amyloid fibrils, and for this reason it is widely used as a model system to study fibril formation mechanisms. In this work, we focused on insulin aggregation mechanisms occurring in HCl solutions (pH 1.6) at 60 degrees C. By means of in situ Thioflavin T (ThT) staining, the kinetics profiles were characterized as a function of the protein concentration, and two concurrent aggregation pathways were pointed out, being concentration dependent. In correspondence to these pathways, different morphologies of self-assembled protein molecules were detected by atomic force microscopy images also evidencing the prese…
Characterization of the nucleation process of lysozyme at physiological pH: Primary but not sole process
2013
We report on a kinetic study of the heat-induced aggregation process of lysozyme at physiological pH. The time evolution of the aggregation extent and the conformational changes of the protein were followed by dynamic light scattering (DLS) and FTIR spectroscopy, respectively, whereas the morphology of the aggregates was observed by Atomic Force Microscopy (AFM). The conformational changes of the secondary and tertiary structures were simultaneous and distinct in time with respect to the formation of aggregates. Oligomer formation occurred through at least two different aggregation processes: a nucleation process and a homogeneous non-nucleative diffusion-controlled process. FTIR measuremen…
Oxidation Enhances Human Serum Albumin Thermal Stability and Changes the Routes of Amyloid Fibril Formation
2014
Oxidative damages are linked to several aging-related diseases and are among the chemical pathways determining protein degradation. Specifically, interplay of oxidative stress and protein aggregation is recognized to have a link to the loss of cellular function in pathologies like Alzheimer's and Parkinson's diseases. Interaction between protein and reactive oxygen species may indeed induce small changes in protein structure and lead to the inhibition/modification of protein aggregation process, potentially determining the formation of species with different inherent toxicity. Understanding the temperate relationship between these events can be of utmost importance in unraveling the molecul…