scholarly journals Protein Solubility Predictions Using the CamSol Method in the Study of Protein Homeostasis

2019 ◽  
Vol 11 (12) ◽  
pp. a033845 ◽  
Author(s):  
Pietro Sormanni ◽  
Michele Vendruscolo
2019 ◽  
Author(s):  
Xiaojing Sui ◽  
Douglas E. V. Pires ◽  
Shuai Nie ◽  
Giulia Vecchi ◽  
Michele Vendruscolo ◽  
...  

ABSTRACTThe accumulation of protein deposits in neurodegenerative diseases involves the presence of a metastable subproteome vulnerable to aggregation. To investigate this subproteome and the mechanisms that regulates it, we measured the proteome solubility of the Neuro2a cell line under protein homeostasis stresses induced by Huntington Disease proteotoxicity; Hsp70, Hsp90, proteasome and ER-mediated folding inhibition; and oxidative stress. We found one-quarter of the proteome extensively changed solubility. Remarkably, almost all the increases in insolubility were counteracted by increases in solubility of other proteins. Each stress directed a highly specific pattern of change, which reflected the remodelling of protein complexes involved in adaptation to perturbation, most notably stress granule proteins, which responded differently to different stresses. These results indicate that the robustness of protein homeostasis relies on the absence of proteins highly vulnerable to aggregation and on large changes in aggregation state of regulatory mechanisms that restore protein solubility upon specific perturbations.


2019 ◽  
Vol 19 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Mariana B. de Oliveira ◽  
Luiz F.G. Sanson ◽  
Angela I.P. Eugenio ◽  
Rebecca S.S. Barbosa-Dantas ◽  
Gisele W.B. Colleoni

Introduction:Multiple myeloma (MM) cells accumulate in the bone marrow and produce enormous quantities of immunoglobulins, causing endoplasmatic reticulum stress and activation of protein handling machinery, such as heat shock protein response, autophagy and unfolded protein response (UPR).Methods:We evaluated cell lines viability after treatment with bortezomib (B) in combination with HSP70 (VER-15508) and autophagy (SBI-0206965) or UPR (STF- 083010) inhibitors.Results:For RPMI-8226, after 72 hours of treatment with B+VER+STF or B+VER+SBI, we observed 15% of viable cells, but treatment with B alone was better (90% of cell death). For U266, treatment with B+VER+STF or with B+VER+SBI for 72 hours resulted in 20% of cell viability and both treatments were better than treatment with B alone (40% of cell death). After both triplet combinations, RPMI-8226 and U266 presented the overexpression of XBP-1 UPR protein, suggesting that it is acting as a compensatory mechanism, in an attempt of the cell to handle the otherwise lethal large amount of immunoglobulin overload.Conclusion:Our in vitro results provide additional evidence that combinations of protein homeostasis inhibitors might be explored as treatment options for MM.


2019 ◽  
Vol 15 (3) ◽  
pp. 228-233
Author(s):  
Prabhavathi Supriya ◽  
Kandikere R. Sridhar

Background: Utilization of wild legumes has received prime importance in the recent past to compensate the scarcity of protein-rich foods as well as to tackle the protein energy malnutrition. Ripened split beans of Canavalia maritima devoid of seed coat and testa serve as traditional nutraceutical source for the coastal dwellers of Southwest India. Objective: The present study projects proximal and functional attributes of uncooked and cooked ripened split beans of C. maritima to be used in the preparation of functional foods. Methods: Proximal properties (moisture, crude protein, total lipids, crude fibre, carbohydrates and calorific value) and functional properties (protein solubility, gelation capacity, water-absorption, oilabsorption, emulsion qualities and foam qualities) of split beans were evaluated by standard methods. Results: Cooking did not significantly changed the crude protein, total lipids, ash, carbohydrates and calorific value, while it significantly increased the crude fibre. The protein solubility, water-absorption capacity, foam capacity and foam stability were significantly higher in uncooked than cooked beans. The cooked beans were superior to uncooked beans in least gelation concentration, low oil-absorption capacity, emulsion activity and emulsion stability. Conclusion: The functional properties of split bean flours were influenced by the proximal components like crude protein, total lipids and crude fibre. The energy-rich ripened split beans of C. maritima can serve as a new potential source for production of value added functional foods owing to their rich protein, rich carbohydrates, low-lipid and potential bioactive attributes.


Sign in / Sign up

Export Citation Format

Share Document