Structural and dynamical determinants of a β-sheet-enriched intermediate involved in amyloid fibrillar assembly of human prion protein

Russo, Luigi; Salzano, Giulia; Andrea, Corvino; Bistaffa, Edoardo; Moda, Fabio; Celauro, Luigi; D’Abrosca, Gianluca; Isernia, Carla; Milardi, Danilo; Giachin, Gabriele; Malgieri, Gaetano; Legname, Giuseppe; Fattorusso, Roberto

doi:10.1039/d2sc00345g

Cited by 3 publications

(1 citation statement)

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“…PHOX2B-20A contains a compact globular HD domain and a highly dynamic C-terminal domain that bears a polyAla sequence forming a helical structure. The PHOX2B-20A structural and dynamical behaviour described here indicates that the two domains very likely cross-talk through transient interactions: 56 the C-terminal tail transiently interacts with the HD without altering its tertiary organization.…”

Section: Discussionmentioning

confidence: 86%

Structural characterization of PHOX2B and its DNA interaction shed light on the molecular basis of the +7Ala variant pathogenicity in CCHS

Diana,

Pirone,

Russo

et al. 2024

Chem. Sci.

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Section: Discussionmentioning

confidence: 86%

Structural characterization of PHOX2B and its DNA interaction shed light on the molecular basis of the +7Ala variant pathogenicity in CCHS

Diana,

Pirone,

Russo

et al. 2024

Chem. Sci.

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Nuclear spin relaxation

Kowalewski

2023

Nuclear Magnetic Resonance

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This review covers the progress in the field of NMR relaxation in fluids during 2022. The emphasis is on comparatively simple liquids and solutions of physico-chemical and chemical interest, in analogy with the previous periods, but selected biophysics-related topics (here, I also include some work on relaxation in solid biomaterials) and relaxation-related studies on more complex systems (macromolecular solutions, liquid crystalline systems, glassy and porous materials) are also covered. Section 2 of the chapter is concerned with general, physical and experimental aspects of nuclear spin relaxation, while Section 3 is concentrated on applications.

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Unfolding Mechanism and Fibril Formation Propensity of Human Prion Protein in the Presence of Molecular Crowding Agents

Madheswaran,

Ventserova,

D’Abrosca

et al. 2024

IJMS

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The pathological process of prion diseases implicates that the normal physiological cellular prion protein (PrPC) converts into misfolded abnormal scrapie prion (PrPSc) through post-translational modifications that increase β-sheet conformation. We recently demonstrated that HuPrP(90–231) thermal unfolding is partially irreversible and characterized by an intermediate state (β-PrPI), which has been revealed to be involved in the initial stages of PrPC fibrillation, with a seeding activity comparable to that of human infectious prions. In this study, we report the thermal unfolding characterization, in cell-mimicking conditions, of the truncated (HuPrP(90–231)) and full-length (HuPrP(23–231)) human prion protein by means of CD and NMR spectroscopy, revealing that HuPrP(90–231) thermal unfolding is characterized by two successive transitions, as in buffer solution. The amyloidogenic propensity of HuPrP(90–231) under crowded conditions has also been investigated. Our findings show that although the prion intermediate, structurally very similar to β-PrPI, forms at a lower temperature compared to when it is dissolved in buffer solution, in cell-mimicking conditions, the formation of prion fibrils requires a longer incubation time, outlining how molecular crowding influences both the equilibrium states of PrP and its kinetic pathways of folding and aggregation.

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Structural and dynamical determinants of a β-sheet-enriched intermediate involved in amyloid fibrillar assembly of human prion protein

Abstract: The conformational conversion of the cellular prion protein (PrPC) into misfolded, aggregated and infectious scrapie isoform is associated with prion disease pathology and neurodegeneration. Despite the significant number of experimental...

Cited by 3 publications

References 100 publications

Structural characterization of PHOX2B and its DNA interaction shed light on the molecular basis of the +7Ala variant pathogenicity in CCHS

Structural characterization of PHOX2B and its DNA interaction shed light on the molecular basis of the +7Ala variant pathogenicity in CCHS

Nuclear spin relaxation

Unfolding Mechanism and Fibril Formation Propensity of Human Prion Protein in the Presence of Molecular Crowding Agents

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