Search results for "Protein Stability"
showing 10 items of 62 documents
Oligomerization of polytopic α-helical membrane proteins: causes and consequences
2012
Abstract Several polytopic α-helical membrane-integrated proteins appear to be organized in higher-ordered oligomeric complexes. While many aspects are still enigmatic, in recent years, the physiological impact of membrane protein oligomerization has been analyzed to some extent. In the present article, oligomerization of structurally well-defined membrane proteins is discussed. The available experimental information indicates the causes and physiological consequences of membrane protein oligomerization, including stabilization, cooperative functions, and control of specific activities. Based on the currently available observations, we aim to derive some general principles and discuss open …
Thermostability of Two Cyanobacterial GrpE Thermosensors
2011
GrpE proteins act as co-chaperones for DnaK heat-shock proteins. The dimeric protein unfolds under heat stress conditions, which results in impaired interaction with a DnaK protein. Since interaction of GrpE with DnaK is crucial for the DnaK chaperone activity, GrpE proteins act as a thermosensor in bacteria. Here we have analyzed the thermostability and function of two GrpE homologs of the mesophilic cyanobacterium Synechocystis sp. PCC 6803 and of the thermophilic cyanobacterium Thermosynechococcus elongatus BP1. While in Synechocystis an N-terminal helix pair of the GrpE dimer appears to be the thermosensing domain and mainly mediates GrpE dimerization, the C-terminal four-helix bundle i…
SUMOylation of Blimp-1 promotes its proteasomal degradation
2011
Abstract B lymphocyte induced maturation protein-1 (Blimp-1) is a transcription repressor of the Krueppel-like family. Blimp-1 plays important roles in developmental processes, such as of germ cells and hair follicle stem cells. In B lymphocytes Blimp-1 orchestrates the terminal differentiation into plasma cells. We discovered that Blimp-1 undergoes SUMOylation by SUMO-1. This SUMOylation is modulated by the SUMO protease SENP1. While Blimp-1 is relatively stable in 293T cells, a fusion with SUMO1 rendered it to rapid proteasomal degradation. Increase in SENP1 activity stabilized Blimp-1, while a decrease promoted its degradation. Our data indicate that SUMOylation of Blimp-1 regulates its …
Biotechnical applications of small heat shock proteins from bacteria.
2012
The stress responses of most bacteria are thought to involve the upregulation of small heat shock proteins. We describe here some of the most pertinent aspects of small heat shock proteins, to highlight their potential for use in various applications. Bacterial species have between one and 13 genes encoding small heat shock proteins, the precise number depending on the species considered. Major efforts have recently been made to characterize the protein protection and membrane stabilization mechanisms involving small heat shock proteins in bacteria. These proteins seem to be involved in the acquisition of cellular heat tolerance. They could therefore potentially be used to maintain cell via…
Thioflavin T templates amyloid β(1–40) conformation and aggregation pathway
2015
Aβ(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies to control the occurring events. To this purpose the exploitation of small molecules interacting with Aβ aggregation represents one of the possible routes. Moreover, the use specific labeling has represented so far one of the most common and effective methods to investigate such a process. This possibility in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effe…
Atomic mean square displacements in proteins by Molecular Dynamics: a case for analysis of variance
2004
Information on protein internal motions is usually obtained through the analysis of atomic mean-square displacements, which are a measure of variability of the atomic positions distribution functions. We report a statistical approach to analyze molecular dynamics data on these displacements that is based on probability distribution functions. Using a technique inspired by the analysis of variance, we compute unbiased, reliable mean-square displacements of the atoms and analyze them statistically. We applied this procedure to characterize protein thermostability by comparing the results for a thermophilic enzyme and a mesophilic homolog. In agreement with previous experimental observations, …
Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity
2012
Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe…
Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation
2015
Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PI…
Effective approach for calculations of absolute stability of proteins using focused dielectric constants
2009
The ability to predict the absolute stability of proteins based on their corresponding sequence and structure is a problem of great fundamental and practical importance. In this work, we report an extensive, refinement and validation of our recent approach (Roca et al., FEBS Lett 2007;581:2065-2071) for predicting absolute values of protein stability DeltaG(fold). This approach employs the semimacroscopic protein dipole Langevin dipole method in its linear response approximation version (PDLD/S-LRA) while using the best fitted values of the dielectric constants epsilon'(p) and epsilon'(eff) for the self energy and charge-charge interactions, respectively. The method is validated on a divers…
New set of 2D/3D thermodynamic indices for proteins. A formalism based on "Molten Globule" theory
2010
Abstract We define eight new macromolecular indices, and several related descriptors for proteins. The coarse grained methodology used for its deduction ensures its fast execution and becomes a powerful potential tool to explore large databases of protein structures. The indices are intended for stability studies, predicting Φ -values, predicting folding rate constants, protein QSAR/QSPR as well as protein alignment studies. Also, these indices could be used as scoring function in protein-protein docking or 3D protein structure prediction algorithms and any others applications which need a numerical code for proteins and/or residues from 2D or 3D format.