Publications by authors named "Romeo C A Dubini"

3 Publications

  • Page 1 of 1

Hydration-Induced Structural Transitions in Biomimetic Tandem Repeat Proteins.

J Phys Chem B 2021 03 17;125(8):2134-2145. Epub 2021 Feb 17.

Faculty of Chemistry and Pharmacy, Department of Chemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.

A major challenge in developing biomimetic, high-performance, and sustainable products is the accurate replication of the biological materials' striking properties, such as high strength, self-repair, and stimuli-responsiveness. The rationalization of such features on the microscopic scale, together with the rational design of synthetic materials, is currently hindered by our limited understanding of the sequence-structure-property relationship. Here, employing state-of-the-art nuclear magnetic resonance (NMR) spectroscopy, we link the atomistic structural and dynamic properties of an artificial bioinspired tandem repeat protein TR(1,11) to its stunning macroscopic properties including high elasticity, self-healing capabilities, and record-holding proton conductivity among biological materials. We show that the hydration-induced structural rearrangement of the amorphous Gly-rich soft segment and the ordered Ala-rich hard segment is the key to the material's outstanding physical properties. We found that in the hydrated state both the Ala-rich ordered and Gly-rich disordered parts contribute to the formation of the nanoconfined β-sheets, thereby enhancing the strength and toughness of the material. This restructuring is accompanied by fast proline ring puckering and backbone - isomerization at the water-protein interface, which in turn enhances the elasticity and the thermal conductivity of the hydrated films. Our in-depth characterization provides a solid ground for the development of next-generation materials with improved properties.
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http://dx.doi.org/10.1021/acs.jpcb.0c11505DOI Listing
March 2021

Small molecule induced toxic human-IAPP species characterized by NMR.

Chem Commun (Camb) 2020 Nov 2;56(86):13129-13132. Epub 2020 Oct 2.

Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.

In this study, the effect of CurDAc, a water-soluble curcumin derivative, on the formation and stability of amyloid fibers is revealed. CurDAc interaction with amyloid is structurally selective, which is reflected in a strong interference with hIAPP aggregation while showing weaker interactions with human-calcitonin and amyloid-β in comparison. Remarkably, CurDAc also exhibited potent fiber disaggregation for hIAPP generating a toxic oligomeric species.
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http://dx.doi.org/10.1039/d0cc04803hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641245PMC
November 2020

Impact of 5-formylcytosine on the melting kinetics of DNA by 1H NMR chemical exchange.

Nucleic Acids Res 2020 09;48(15):8796-8807

Faculty of Chemistry and Pharmacy, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany.

5-Formylcytosine (5fC) is a chemically edited, naturally occurring nucleobase which appears in the context of modified DNA strands. The understanding of the impact of 5fC on dsDNA physical properties is to date limited. In this work, we applied temperature-dependent 1H Chemical Exchange Saturation Transfer (CEST) NMR experiments to non-invasively and site-specifically measure the thermodynamic and kinetic influence of formylated cytosine nucleobase on the melting process involving dsDNA. Incorporation of 5fC within symmetrically positioned CpG sites destabilizes the whole dsDNA structure-as witnessed from the ∼2°C decrease in the melting temperature and 5-10 kJ mol-1 decrease in ΔG°-and affects the kinetic rates of association and dissociation. We observed an up to ∼5-fold enhancement of the dsDNA dissociation and an up to ∼3-fold reduction in ssDNA association rate constants, over multiple temperatures and for several proton reporters. Eyring and van't Hoff analysis proved that the destabilization is not localized, instead all base-pairs are affected and the transition states resembles the single-stranded conformation. These results advance our knowledge about the role of 5fC as a semi-permanent epigenetic modification and assist in the understanding of its interactions with reader proteins.
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http://dx.doi.org/10.1093/nar/gkaa589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470965PMC
September 2020