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Noemi Ferrante Carrante. Portrait.

Noemi Ferrante Carrante

Doctoral student

Noemi Ferrante Carrante. Portrait.

On the transient interactions of α-synuclein in different dimensions

Author

  • L. Ortigosa-Pascual
  • N. Ferrante-Carrante
  • K. Bernfur
  • K. Makasewicz
  • E. Sparr
  • S. Linse

Summary, in English

α-Synuclein (αSyn) is a neuronal protein predominantly found in the brain, whose native function seems to be associated with vesicle trafficking. While intrinsically disordered in solution, the first ca. 100 residues adopt an amphipathic α-helical structure when the protein adsorbs onto membranes. Additionally, the aggregation of αSyn into highly ordered β-sheet rich amyloid fibrils is associated with Parkinson′s disease. The different regions of αSyn and the interactions between them have been reported to play a key role in the behaviour of the protein in solution, its membrane binding, and its aggregation into fibrils. This study employs photo-induced cross-linking of unmodified proteins (PICUP) to capture and identify the transient contacts of αSyn in different conformational states: free in solution, adsorbed to membranes, and aggregated into fibrils. By using tyrosine-to-phenylalanine mutations to block the reactivity of specific amino acid residues, we establish key cross-links in each state. In solution, we identify internal contacts between the N and C termini of monomers, as well as inter-monomer contacts between C termini in oligomers. When αSyn is adsorbed to membranes, the internal cross-linking is blocked, while cross-linking between C-terminal regions persists. In fibrils, cross-linking is significantly reduced, primarily occurring between C-terminal residues of adjacent monomers. This work highlights the utility of PICUP for reporting on the transient contacts that occur on the pathways of self- and co-assembly of αSyn.

Department/s

  • Biochemistry and Structural Biology
  • Physical Chemistry
  • MultiPark: Multidisciplinary research on neurodegenerative diseases
  • LU Profile Area: Light and Materials
  • LU Profile Area: Proactive Ageing
  • LTH Profile Area: Nanoscience and Semiconductor Technology
  • NanoLund: Centre for Nanoscience

Publishing year

2025

Language

English

Document type

Preprint

Publisher

bioRxiv

Topic

  • Biological Sciences

Status

Published