Search results for "Folding"
showing 10 items of 330 documents
Nucleation and Growth of CaCO3 Mediated by the Egg-White Protein Ovalbumin: A Time-Resolved in situ Study Using Small-Angle Neutron Scattering
2008
Mineralization of calcium carbonate in aqueous solutions starting from its initiation was studied by time-resolved small-angle neutron scattering (SANS). SANS revealed that homogeneous crystallization of CaCO 3 involves an initial formation of thin plate-shaped nuclei which subsequently reassemble to 3-dimensional particles, first of fractal and finally of compact structure. The presence of the egg-white protein ovalbumin leads to a different progression of mineralization through several stages; the first step represents amorphous CaCO 3, whereas the other phases are crystalline. The formation and dissolution of the amorphous phase is accompanied by Ca (2+)-mediated unfolding and cross-link…
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…
Targeting heat shock proteins in cancer
2010
Heat shock proteins (HSPs) HSP27, HSP70 and HSP90 are powerful chaperones. Their expression is induced in response to a wide variety of physiological and environmental insults including anti-cancer chemotherapy, thus allowing the cell to survive to lethal conditions. Different functions of HSPs have been described to account for their cytoprotective function, including their role as molecular chaperones as they play a central role in the correct folding of misfolded proteins, but also their anti-apoptotic properties. HSPs are often overexpressed in cancer cells and this constitutive expression is necessary for cancer cells' survival. HSPs may have oncogene-like functions and likewise mediat…
Ohjaava opetuskeskustelu suomalaisella viittomakielellä : tapaustutkimus kuuron oppilaan matematiikan opetuksesta
2014
Suomalaisen viittomakielen pro gradu –työssäni tarkastelen kuuron oppilaan viittomakielistä opetusta vuorovaikutuksen näkökulmasta. Tutkimusaineisto koostuu kahdesta matematiikan yksilöopetustunnista. Tutkimuksen tavoitteena on ollut selvittää, millaisia muotoja ohjaava opetuskeskustelu saa kuuron oppilaan suomalaisella viittomakielellä toteutetussa opetuksessa. Tapaustutkimuksen kautta yksilöidään ja luokitellaan myös viittomakielisen ohjaavan opetuskeskustelun osatekijöitä. Tutkimusaineiston analyysi perustuu Vygotskyn (1978) sosiokulttuuriseen teoriaan ja siihen liittyviin käsitteisiin oppimisen oikea-aikainen tukeminen ja lähikehityksen vyöhyke. Videotaltiointien analy…
The role of heat shock proteins in neoplastic processes and the research on their importance in the diagnosis and treatment of cancer
2021
Heat shock proteins (HSPs) are chaperones with highly conservative primary structure, necessary in the processes of protein folding to the most energetically advantageous conformation and maintaining their stability. HSPs perform a number of important functions in various cellular processes and are capable of modulating pathophysiological conditions at the cellular and systemic levels. An example is the high level of HSP expression in neoplastic tissues, which disrupts the apoptosis of transformed cells and promotes the processes of proliferation, invasion, and metastasis. In addition, an increasing amount of information is appearing about the participation of HSPs in the formation of multi…
Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk
2019
Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unusually high content of the amino acid methionine. We simultaneously mutate all methionines present in the hydrophobic core of a spidroin NTD from a nursery web spider’s dragline silk to leucine. The mutated NTD is strongly stabilized and folds at the theoretical speed limit. The structure of the mutant is preserved, yet its ability to dimerize is substantially impaired. We find that side chains of…
A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model
2014
Chaperonins mediate protein folding in a cavity formed by multisubunit rings. The human CCT has eight non-identical subunits and the His147Arg mutation in one subunit, CCT5, causes neuropathy. Knowledge is scarce on the impact of this and other mutations upon the chaperone's structure and functions. To make progress, experimental models must be developed. We used an archaeal mutant homolog and demonstrated that the His147Arg mutant has impaired oligomeric assembly, ATPase activity, and defective protein homeostasis functions. These results establish for the first time that a human chaperonin gene defect can be reproduced and studied at the molecular level with an archaeal homolog. The major…
Tubulin-folding cofactor E deficiency is associated with vascular dysfunction and endoplasmatic reticulum stress of vascular smooth muscle cells
2021
Abstract Introduction Endothelial function assessed via flow mediated dilatation (FMD) has shown to predict risk in individuals with established cardiovascular diseases, whereas its predictive value is uncertain in the setting primary prevention. Purpose The aim of the current work was to discover and evaluate novel mediators of vascular dysfunction in the general population and in conditional knock-out transgenic animal models. Methods In order to identify novel targets that were negatively correlated with FMD and investigate their contribution in vascular function, a Genome Wide Association Study (GWAS) of 5,000 participants was performed and subsequently immune cell-, endothelial- and va…
The tetrameric α-helical membrane protein GlpF unfolds via a dimeric folding intermediate.
2011
Many membrane proteins appear to be present and functional in higher-order oligomeric states. While few studies have analyzed the thermodynamic stability of α-helical transmembrane (TM) proteins under equilibrium conditions in the past, oligomerization of larger polytopic monomers has essentially not yet been studied. However, it is vital to study the folding of oligomeric membrane proteins to improve our understanding of the general mechanisms and pathways of TM protein folding. To investigate the folding and stability of the aquaglyceroporin GlpF from Escherichia coli, unfolding of the protein in mixed micelles was monitored by steady-state fluorescence and circular dichroism spectroscopy…
Nested MWC model describes hydrolysis of GroEL without assuming negative cooperativity in binding
2002
Folding assistance and ATPase activity of GroEL are based on the existence of different conformations. In order to characterise these conformations, published data on steady state ATPase activity in the absence of GroES were reanalysed simultaneously in terms of the Nested MWC model. This model is a hierarchical extension of the symmetry-model of Monod et al. [J. Mol. Biol. 12 (1965) 88]. An unique set of GroEL specific parameters was obtained. This set was supported by comparison of predictions arising from this set of values with experimental data for hydrolysis of ATP in the presence of ADP and ATPgammaS, binding of ATPgammaS and ADP to GroEL in the absence of ATP, and binding of ATP as …