Untangling the interaction of α-synuclein with DNA i-motifs and hairpins by volume-sensitive single-molecule FRET spectroscopy

Mukherjee, Sumitava; Knop, Jim‐Marcel; Oliva, Rosario; Möbitz, Simone; Winter, Roland

doi:10.1039/d1cb00108f

Cited by 9 publications

(8 citation statements)

References 55 publications

(89 reference statements)

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“…The volumetric properties of protein–nucleic acid interactions can also be effectively investigated by smFRET [ 22 ]. After the successful characterization of the main molecular components of the living systems, the description of their interactions could be a promising direction.…”

Section: Pressure Effect On Some Biomoleculesmentioning

confidence: 99%

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Biomolecules under Pressure: Phase Diagrams, Volume Changes, and High Pressure Spectroscopic Techniques

Smeller

2022

IJMS

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Pressure is an equally important thermodynamical parameter as temperature. However, its importance is often overlooked in the biophysical and biochemical investigations of biomolecules and biological systems. This review focuses on the application of high pressure (>100 MPa = 1 kbar) in biology. Studies of high pressure can give insight into the volumetric aspects of various biological systems; this information cannot be obtained otherwise. High-pressure treatment is a potentially useful alternative method to heat-treatment in food science. Elevated pressure (up to 120 MPa) is present in the deep sea, which is a considerable part of the biosphere. From a basic scientific point of view, the application of the gamut of modern spectroscopic techniques provides information about the conformational changes of biomolecules, fluctuations, and flexibility. This paper reviews first the thermodynamic aspects of pressure science, the important parameters affecting the volume of a molecule. The technical aspects of high pressure production are briefly mentioned, and the most common high-pressure-compatible spectroscopic techniques are also discussed. The last part of this paper deals with the main biomolecules, lipids, proteins, and nucleic acids: how they are affected by pressure and what information can be gained about them using pressure. I I also briefly mention a few supramolecular structures such as viruses and bacteria. Finally, a subjective view of the most promising directions of high pressure bioscience is outlined.

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Section: Pressure Effect On Some Biomoleculesmentioning

confidence: 99%

“…With the appearance of new sophisticated microscopic techniques, new possibilities emerged for scientists interested in high pressure studies. Measuring single molecular changes under pressure is one of these cutting-edge applications of modern microscopic methods in the high pressure field [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Biomolecules under Pressure: Phase Diagrams, Volume Changes, and High Pressure Spectroscopic Techniques

Smeller

2022

IJMS

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“…NMR spectroscopy demonstrates that the same N-terminal domain that binds curved, negatively charged phospholipid membranes mediates aSyn’s binding to the phosphate backbone of DNA ( 7 ). Single-molecule techniques have shown that aSyn binding can stretch DNA and increase its stiffness ( 51 , 52 ), while fluorescence resonance energy transfer (FRET) assays developed to study noncanonical DNA structures show that aSyn stabilizes intermediate states on the pathway to DNA hairpin formation ( 53 ) and can bind to i-motifs ( 54 ). Although this work has started to reveal the mechanism of aSyn binding to DNA, important questions remain, including the role of potential disease-relevant aSyn posttranslational modifications in this process.…”

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confidence: 99%

Phosphorylation of the aggregate-forming protein alpha-synuclein on serine-129 inhibits its DNA-bending properties

Dent

King

Osterberg

et al. 2022

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…A sm-FRET study revealed that the conformational landscape of i-motifs is markedly affected by the presence of α-synuclein, an amyloidogenic protein being responsible for Parkinson’s disease. Volumetric data obtained from pressure-axis experiments demonstrated that the complex formed between monomeric α-synuclein with the i-motif is densely packed and hence pressure-stable, whereas a negative volume change of −54 mL mol –1 was obtained for the interaction of aggregated oligomeric α-synuclein with the i-motif, pointing to a loose unspecific binding . Merrin et al studied binding of RecA protein to ssDNA in the presence of ATP .…”

Section: Resultsmentioning

confidence: 99%

“…Volumetric data obtained from pressure-axis experiments demonstrated that the complex formed between monomeric α-synuclein with the i-motif is densely packed and hence pressure-stable, whereas a negative volume change of −54 mL mol −1 was obtained for the interaction of aggregated oligomeric α-synuclein with the imotif, pointing to a loose unspecific binding. 213 Merrin et al studied binding of RecA protein to ssDNA in the presence of ATP. 211 Experiments were performed on E. coli RecA and RecA from a thermophilic bacterium, Thermus thermophilus, and it was found that binding for T. thermophilus RecA occurs for a wider range of temperature and pressures, suggesting a correlation between thermophilicity and barophilicity, i.e., adaptation to temperature and pressure at the single protein level.…”

Section: Effect Of Hydrostatic and Osmotic Pressure On Nucleic Acid S...mentioning

confidence: 99%

Life in Multi-Extreme Environments: Brines, Osmotic and Hydrostatic Pressure─A Physicochemical View

et al. 2022

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Elucidating the details of the formation, stability, interactions, and reactivity of biomolecular systems under extreme environmental conditions, including high salt concentrations in brines and high osmotic and high hydrostatic pressures, is of fundamental biological, astrobiological, and biotechnological importance. Bacteria and archaea are able to survive in the deep ocean or subsurface of Earth, where pressures of up to 1 kbar are reached. The deep subsurface of Mars may host high concentrations of ions in brines, such as perchlorates, but we know little about how these conditions and the resulting osmotic stress conditions would affect the habitability of such environments for cellular life. We discuss the combined effects of osmotic (salts, organic cosolvents) and hydrostatic pressures on the structure, stability, and reactivity of biomolecular systems, including membranes, proteins, and nucleic acids. To this end, a variety of biophysical techniques have been applied, including calorimetry, UV/vis, FTIR and fluorescence spectroscopy, and neutron and X-ray scattering, in conjunction with high pressure techniques. Knowledge of these effects is essential to our understanding of life exposed to such harsh conditions, and of the physical limits of life in general. Finally, we discuss strategies that not only help us understand the adaptive mechanisms of organisms that thrive in such harsh geological settings but could also have important ramifications in biotechnological and pharmaceutical applications.

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Untangling the interaction of α-synuclein with DNA i-motifs and hairpins by volume-sensitive single-molecule FRET spectroscopy

Abstract: The intrinsically disordered protein α-synuclein causes Parkinson’s disease by forming toxic oligomeric aggregates inside neurons. Single-molecule FRET experiments revealed conformational changes of noncanonical DNA structures, such as i-motifs and hairpins,...

Cited by 9 publications

References 55 publications

Biomolecules under Pressure: Phase Diagrams, Volume Changes, and High Pressure Spectroscopic Techniques

Biomolecules under Pressure: Phase Diagrams, Volume Changes, and High Pressure Spectroscopic Techniques

Phosphorylation of the aggregate-forming protein alpha-synuclein on serine-129 inhibits its DNA-bending properties

Life in Multi-Extreme Environments: Brines, Osmotic and Hydrostatic Pressure─A Physicochemical View

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