Harnessing Pressure-Axis Experiments to Explore Volume Fluctuations, Conformational Substates, and Solvation of Biomolecular Systems

Oliva, Rosario; Winter, Roland

doi:10.1021/acs.jpclett.2c03186

Cited by 9 publications

(12 citation statements)

References 105 publications

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“…The application of pressure has the potential to yield additional information about the prevalent intermolecular forces underlying the aggregate formation as the balance between hydrogen bonding, electrostatic and hydrophobic intra- and intermolecular interactions can be tuned by pressure modulation. − H-bonds are generally strengthened upon pressurization, whereas salt bridges are destabilized by high pressure. The dissociation of protein aggregates and unfolding of proteins are also due to the existence of internal voids and packing defects of these structures, leading, in accordance with Le Châtelier’s principle, to an overall volume decrease upon unfolding. ,,, The abundance of ionic interactions between K n and ATP within the aggregates is expected to render them sensitive to high pressure due to the phenomenon of electrostriction ( i.e. , polar water molecules being packed more tightly around separated charges than around nondissociated salt bridges), i.e.…”

Section: Resultsmentioning

confidence: 92%

“…The dissociation of protein aggregates and unfolding of proteins are also due to the existence of internal voids and packing defects of these structures, leading, in accordance with Le Chatelier's principle, to an overall volume decrease upon unfolding. 34,35,40,41 The abundance of ionic interactions between K n and ATP within the aggregates is expected to render them sensitive to high pressure due to the phenomenon of electrostriction (i.e., polar water molecules being packed more tightly around separated charges than around nondissociated salt bridges), i.e., high pressure favors the dissociation of ion pairs and therefore the disassembly of supramolecular architectures that they support. Packing defects in the more disordered K 40 oligolysine/ATP system, as revealed by the FT-IR data, might contribute to the highpressure sensitivity as well.…”

Section: Resultsmentioning

confidence: 99%

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Liquid-Droplet-Mediated ATP-Triggered Amyloidogenic Pathway of Insulin-Derived Chimeric Peptides: Unraveling the Microscopic and Molecular Processes

et al. 2023

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Disease-associated progression of protein dysfunction is typically determined by an interplay of transition pathways leading to liquid−liquid phase separation (LLPS) and amyloid fibrils. As LLPS introduces another layer of complexity into fibrillization of metastable proteins, a need for tunable model systems to study these intertwined processes has emerged. Here, we demonstrate the LLPS/fibrillization properties of a family of chimeric peptides, ACC 1−13 K n , in which the highly amyloidogenic fragment of insulin (ACC 1−13 ) is merged with oligolysine segments of various lengths (K n , n = 8, 16, 24, 32, 40). LLPS and fibrillization of ACC 1−13 K n are triggered by ATP through Coulombic interactions with K n fragments. ACC 1−13 K 8 and ACC 1−13 K 16 form fibrils after a short lag phase without any evidence of LLPS. However, in the case of the three longest peptides, ATP triggers instantaneous LLPS followed by the disappearance of droplets occurring in-phase with the formation of amyloid fibrils. The kinetics of the phase transition and the stability of mature co-aggregates are highly sensitive to ionic strength, indicating that electrostatic interactions play a pivotal role in selecting the LLPS-fibrillization transition pathway. Densely packed ionic interactions that characterize ACC 1−13 K n −ATP fibrils render them highly sensitive to hydrostatic pressure due to solvent electrostriction, as demonstrated by infrared spectroscopy. Using atomic force microscopy imaging of rapidly frozen samples, we demonstrate that early fibrils form within single liquid droplets, starting at the droplet/bulk interface through the formation of single bent fibers. A hypothetical molecular scenario underlying the emergence of the LLPS-to-fibrils pathway in the ACC 1−13 K n −ATP system has been put forward.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Liquid-Droplet-Mediated ATP-Triggered Amyloidogenic Pathway of Insulin-Derived Chimeric Peptides: Unraveling the Microscopic and Molecular Processes

et al. 2023

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“…From the pressure dependence of K b , it was possible to calculate the volume change accompanying the complexation reaction, [25,26] according to (dln K b /d p ) T =

{-}

Δ V b °/( RT ), where Δ V b ° is the binding volume, which is defined as the difference between the partial molar volume of the ligand‐protein complex and the sum of the partial molar volumes of the ligand and of the protein. According to the Le Châtelier principle, pressure favors the state that occupies the smallest possible overall volume [15,25,26] . Thus, if pressure favors the formation of the complex, Δ V b ° will be negative, and vice versa.…”

Section: Resultsmentioning

confidence: 99%

“…The high‐pressure binding data revealed that the binding volume (Table 1) for the interaction of EA with BSA is positive, indicating that the complex occupies a larger volume with respect to the uncomplexed state. A Δ V b °>0 can be ascribed to an increase of void volume in the binding pocket upon complex formation and/or the release of hydration water to the bulk solvent [15,18,25] . Instead, for IB7‐14, the binding volume is essentially zero, revealing an almost perfect packing between the interacting partners.…”

Section: Discussionmentioning

confidence: 99%

Alcohol‐Induced Conformation Changes and Thermodynamic Signatures in the Binding of Polyphenols to Proline‐Rich Salivary Proteins

Jahmidi‐Azizi,

Oliva,

Winter

2023

Chemistry A European J

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The first contact of polyphenols (tannins) with the human body occurs in the mouth, where they are known to interact with proline‐rich proteins (PRPs). These interactions are important at a sensory level, especially for the development of astringency, but affect also various other biochemical processes. Employing thermodynamic measurements, fluorescence and CD spectroscopy, we investigated the binding process of the prototypical polyphenol ellagic acid (EA) to different IB‐PRPs and BSA, also in the presence of ethanol, which is known to influence tannin–protein interactions. Binding of EA to BSA and the small peptide IB7‐14 is weak, but very strong to IB9‐37. The differences in binding strength and stoichiometry are due to differences in the binding motifs, which also lead to differences in the thermodynamic signatures of the binding process. EA binding to BSA is enthalpy‐driven, whereas binding to both IB7‐14 and IB9‐37 is entropy‐driven. The presence of 10 vol.% EtOH, as present in wines, increases the binding constant of EA with BSA and IB7‐14 drastically, but not that with IB9‐37; however, it changes the binding stoichiometry. These differences can be attributed to the effect of EtOH on the conformation dynamics of the proteins and to changes in hydration properties in alcoholic solution.

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“…At appropriate concentrations, PEG and dextran spontaneously separate, 238 forming droplets enriched in dextran dispersed in a solution of PEG. 44,239,240 The protein BSA and ANS preferentially localize in the dextran-enriched droplets, where the polymer concentration is around 30 wt %. HHP fluorescence spectroscopy binding experiments showed that on average three molecules of ANS molecules bind to one BSA macromolecule (Figure 36B), both at neat buffer conditions and in the ATPS system at ambient pressure.…”

Section: Ligand Bindingmentioning

confidence: 99%

Effects of Crowding and Cosolutes on Biomolecular Function at Extreme Environmental Conditions

Peters,

Oliva,

Caliò

et al. 2023

Chem. Rev.

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The extent of the effect of cellular crowding and cosolutes on the functioning of proteins and cells is manifold and includes the stabilization of the biomolecular systems, the excluded volume effect, and the modulation of molecular dynamics. Simultaneously, it is becoming increasingly clear how important it is to take the environment into account if we are to shed light on biological function under various external conditions. Many biosystems thrive under extreme conditions, including the deep sea and subsea floor crust, and can take advantage of some of the effects of crowding. These relationships have been studied in recent years using various biophysical techniques, including neutron and X-ray scattering, calorimetry, FTIR, UV/Vis and fluorescence spectroscopies. Combining knowledge of the structure and conformational dynamics of biomolecules under extreme conditions, such as temperature, high hydrostatic pressure, and high salinity, we highlight the importance of considering all results in the context of the environment. Here we discuss crowding and cosolute effects on proteins, nucleic acids, membranes, and live cells, and explain how it is possible to experimentally separate crowding-induced effects from other influences. Such findings will contribute to a better understanding of the homeoviscous adaptation of organisms and the limits of life in general.

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Harnessing Pressure-Axis Experiments to Explore Volume Fluctuations, Conformational Substates, and Solvation of Biomolecular Systems

Cited by 9 publications

References 105 publications

Liquid-Droplet-Mediated ATP-Triggered Amyloidogenic Pathway of Insulin-Derived Chimeric Peptides: Unraveling the Microscopic and Molecular Processes

Liquid-Droplet-Mediated ATP-Triggered Amyloidogenic Pathway of Insulin-Derived Chimeric Peptides: Unraveling the Microscopic and Molecular Processes

Alcohol‐Induced Conformation Changes and Thermodynamic Signatures in the Binding of Polyphenols to Proline‐Rich Salivary Proteins

Effects of Crowding and Cosolutes on Biomolecular Function at Extreme Environmental Conditions

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