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      Influence of macromolecular crowding on the charge regulation of intrinsically disordered proteins

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          Abstract

          The coupling between the ionization and conformational properties of two IDPs, histatin-5 and β-amyloid 42, in the presence of neutral and charged crowders is studied by performing semi-grand canonical Monte Carlo simulations.

          Abstract

          In this work we study the coupling between ionization and conformational properties of two IDPs, histatin-5 and β-amyloid 42, in the presence of neutral and charged crowders. The latter is modeled to resemble bovine serum albumin (BSA). With this aim, semi-grand canonical Monte Carlo simulations are performed, so that the IDP charge is a dynamic property, undergoing protonation/deprotonation processes. Both ionization properties (global and specific amino acid charge and binding capacitance) and radius of gyration are analyzed in a large range of pH values and salt concentrations. Without crowder agents, the titration curve of histatin-5, a polycation, is salt-dependent while that of β-amyloid 42, a polyampholyte, is almost unaffected. The salt concentration is found to be particularly relevant at pH values where the protein binding capacitance (directly linked with charge fluctuation) is larger. Upon addition of neutral crowders, charge regulation is observed in histatin-5, while for β-amyloid 42 this effect is very small. The main mechanism for charge regulation is found to be the effective increase in the ionic strength due to the excluded volume. In the presence of charged crowders, a significant increase in the charge of both IDPs is observed in almost all the pH range. In this case, the IDP charge is altered not only by the increase in the effective ionic strength but also by its direct electrostatic interaction with the charged crowders.

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          Amyloid beta: structure, biology and structure-based therapeutic development

          Amyloid beta peptide (Aβ) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β- and γ-secretases. Aβ accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of Aβ are and by what mechanism Aβ causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease. In this paper, we review the structures, biological functions, and neurotoxicity role of Aβ. We also discuss the potential receptors that interact with Aβ and mediate Aβ intake, clearance, and metabolism. Additionally, we summarize the therapeutic developments and recent advances of different strategies for treating Alzheimer's disease. Finally, we will report on the progress in searching for novel, potentially effective agents as well as selected promising strategies for the treatment of Alzheimer's disease. These prospects include agents acting on Aβ, its receptors and tau protein, such as small molecules, vaccines and antibodies against Aβ inhibitors or modulators of β- and γ-secretase; Aβ-degrading proteases; tau protein inhibitors and vaccines; amyloid dyes and microRNAs.
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            Understanding protein non-folding.

            This review describes the family of intrinsically disordered proteins, members of which fail to form rigid 3-D structures under physiological conditions, either along their entire lengths or only in localized regions. Instead, these intriguing proteins/regions exist as dynamic ensembles within which atom positions and backbone Ramachandran angles exhibit extreme temporal fluctuations without specific equilibrium values. Many of these intrinsically disordered proteins are known to carry out important biological functions which, in fact, depend on the absence of a specific 3-D structure. The existence of such proteins does not fit the prevailing structure-function paradigm, which states that a unique 3-D structure is a prerequisite to function. Thus, the protein structure-function paradigm has to be expanded to include intrinsically disordered proteins and alternative relationships among protein sequence, structure, and function. This shift in the paradigm represents a major breakthrough for biochemistry, biophysics and molecular biology, as it opens new levels of understanding with regard to the complex life of proteins. This review will try to answer the following questions: how were intrinsically disordered proteins discovered? Why don't these proteins fold? What is so special about intrinsic disorder? What are the functional advantages of disordered proteins/regions? What is the functional repertoire of these proteins? What are the relationships between intrinsically disordered proteins and human diseases? Copyright 2010 Elsevier B.V. All rights reserved.
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              • Record: found
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              Polymer physics of intracellular phase transitions

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                Author and article information

                Contributors
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                Journal
                SMOABF
                Soft Matter
                Soft Matter
                Royal Society of Chemistry (RSC)
                1744-683X
                1744-6848
                January 28 2021
                2021
                : 17
                : 3
                : 655-669
                Affiliations
                [1 ]Physical Chemistry Unit
                [2 ]Materials Science and Physical Chemistry Department & Research Institute of Theoretical and Computational Chemistry (IQTCUB) of Barcelona University (UB)
                [3 ]Barcelona
                [4 ]Spain
                [5 ]Chemistry Department
                [6 ]Technical School of Agricultural Engineering & AGROTECNIO of Lleida University (UdL)
                [7 ]Lleida
                [8 ]Department of Physics
                [9 ]Norwegian University of Science and Technology (NTNU)
                [10 ]Trondheim
                [11 ]Norway
                Article
                10.1039/D0SM01475C
                b663525f-b666-413a-8245-f47326ba6649
                © 2021

                http://rsc.li/journals-terms-of-use

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                Self URI (article page): http://xlink.rsc.org/?DOI=D0SM01475C

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