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The Stress Response and Stress Proteins
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Martin E. Feder, Dawn A. Parsell, Susan L. Lindquist
Many weak forces help stabilize the native structures of proteins, but the hydrophobic effect is generally considered the dominant force driving folding. In the cell, hydrophobic side chains cause surrounding water molecules to adopt an ordered, lattice-like structure that is entropically very unfavorable. Protein domains begin folding with the collapse of hydrophobic side chains into the “core” of the molecule. This collapse, which occurs on a millisecond time scale, allows these side chains to interact with each other and shields them from the surrounding aqueous environment. On the same time scale, units of secondary structure form, primarily α helices and β sheets. At this stage, the protein has a compact structure, but lacks stable tertiary interactions and is thought to resemble the “molten globule” state observed in some proteins under very specific, mild denaturation conditions. The transition from this structure to the final native structure generally requires 50 ms to a few minutes.23
Biophysical Characterization of Misfolded Oligomeric Protein States During the Very Early Stages of Amyloid Formation
Published in Gilles Grateau, Robert A. Kyle, Martha Skinner, Amyloid and Amyloidosis, 2004
The initial state of PGK and SHaPrP90-232, respectively, is a partially folded monomeric state with a predominant α-helical secondary structure. In both cases the conformation is expanded compared to the native state. In contrast, the initial state of barstar prior to assembly is an oligomer made of 16 monomers in a molten globule-like conformation, the so-called A-state of barstar. An ensemble of oligomers is buildt up by the first reaction stage of PGK and SHaPrP90-232, respectively (see Figure 1). The oligomers of PGK have an average mass of ten monomers with a conformation in a predominant β-sheet structure. The oligomer distribution of SHaPrP90-232 is very heterogeneous with an annular-shaped octamer as smallest product. The whole transition to β-sheet structure is already accomplished. During the second growth stage protofibrils are formed by coalescence of the oligomers delivered by the first stage. Barstar forms already protofibrils as product of the first reaction stage whereby it has to be kept in mind that this misfolding reaction starts already with an oligomeric state. The protofibrils of barstar could be further transformed to long, ribbon-like mature fibrils.
Discovery of drugs that directly target the intrinsically disordered region of the androgen receptor
Published in Expert Opinion on Drug Discovery, 2020
AR-NTD is largely unstructured and described as having limited stable secondary structure which can be induced by interactions with binding partners to increase α-helical content and thereby conforms to a molten-globule-like conformation referred to as ‘collapsed disordered’ [13–15] (Figure 2(a)). This domain is the most abundantly post-translationally modified of the AR and acts as a hub for interactions with many other proteins (Figure 2(b)). Most importantly is interaction of this domain with the basal transcriptional machinery that is necessary for its transcriptional activity. Within AR-NTD is AF-1 which is estimated to have 13% helical secondary structure but this can increase upon interaction with a binding partner [13,14]. AF-1 is comprised of two transactivation units 1 and 5 (Tau-1 and Tau-5). Tau-1 is comprised of amino acid residues 101–370 of which a large number are acidic amino acids. Tau-5 is comprised of amino acid residues 360–485 and is not acidic. Interestingly AR-NTD harbors several repeat regions for glutamine (polyglutamine tract or polyQ), proline, alanine, and glycine.
Dynamic Aspects of the Immunoglobulin Structure
Published in Immunological Investigations, 2019
Immunoglobulin E is an important participant in allergic reactions. The Fcε fragment reacts with the FcεRI receptor on mast cells, and with CD23 on B cells. The Fcε is composed of dimers from the Cε2, Cε3, and Cε4 domains, and is, by nature, flexible (Wurzburg and Jardetzky, 2009). According to crystallographic studies (Drinkwater et al., 2014), the Cε2 domains fold back on the Cε3 and Cε4 domains. The Cε3 domains react with the both cell receptors and thus play a central role in IgE’s biological activity. Isolated Cε3 have a ”molten globule” structure, retaining their flexibility within the IgE molecule (Borthakur et al., 2011; Harwood and McDonnell, 2007; Henry et al., 2000; Price et al., 2005), but is well-structured, following formation of complexes with the FcεRI receptor. The detailed structure of Fcε and its domains was elucidated at the highest resolutions by means of X-ray crystallography and by differential scanning fluorimetric analysis (Doré et al., 2017). It was found that the Cε3 domain displays intrinsic flexibility and quaternary structural variation especially in regions distant from Cε4. The reaction with the cell receptors or corresponding antibodies stabilizes the Cε3 structure. The high-mannose carbohydrate unit of Cε3 is well-ordered and makes contact with Cε4, which is not essential for cell receptor binding.
Magnesium and calcium ions: roles in bacterial cell attachment and biofilm structure maturation
Published in Biofouling, 2019
Tianyang Wang, Steve Flint, Jon Palmer
Other bacteria, including R. leguminosarum, Shewanella oneidensis, S. mutants and P. putida, were also found to adopt a protein-mediated method in assembling biofilms. Unlike S. aureus, they benefit from Ca2+ in forming biofilms. Ca2+ accelerates biofilm development of Pseudomonas putida and also increases the total biomass of biofilm. The C-terminal region of LapF protein, a large secreted protein involved in microcolony formation and biofilm maturation in P. putida, undergoes multimerization by binding Ca2+, which later was proven to be localized, mainly between the biofilm cells. The addition of the calcium chelator EGTA dissolved the aggregates (Martinez-Gil et al. 2012). In the presence of calcium ions, RapA2 folds from a molten globule state into a compact structure that recognizes and binds exopolysaccharides from R. leguminosarum strains (Abdian et al. 2013), resulting in the development of biofilm matrix on the roots of plants. Various other calcium-binding proteins that are involved in biofilm formation have being reported and are listed in Table 1.