Seminarios

¡CANCELADO! "On the structure and membrane-binding properties of oligomeric species of the Parkinson´s disease related protein alpha-synuclein" Dra. M. Soledad Celej

Resumen:
 

Amyloid deposits of the presynaptic protein alpha-synuclein (AS) are pathognomonic of Parkinson's disease, a  neurodegenerative movement disorder associated with axon degeneration of dopaminergic nigral neurons. Prefibrillar AS oligomers (oAS) are highly neurotoxic since they might damage synapses and dendrites by both altering the physiological function of AS and acting as active pathogenic species. Despite the role of these species is disease, little is known about their structure or molecular basis of their biological activity. First, we used a combination of ATR-FTIR spectroscopy and site-specific fluorescence to interrogate about the beta-sheet organization within oAS. We showed that oAS adopt a distinct antiparallel beta-sheet structure, as opposed to the parallel cross-beta fibrillar fold1 and that they are ordered assemblies possessing a well-defined pattern of intermolecular contacts2. These antiparallel beta-sheet intermediates are built-up at early stages of aggregation, which then evolve to parallel beta-sheet fibrils through helix-rich/disordered species3. Then, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oAS to lipid vesicles of different curvatures and  compositions4. We found that AS oligomerization has a profound impact on protein-lipid interaction, altering binding affinity  and/or curvature sensitivity depending on membrane composition. Our work provides novel for the understanding of the  molecular bases underlying AS pathology.

Acknowledgements: Agencia-FONCyT, CONICET, SECyT-UNC, Fundación Florencio Fiorini, ISN-CAEN, Fulbright-CONICET, CONICET-FNRS and MINCyT-FNRS for financial support.

References

  1. Celej MS et al, Biochem. J. 2012, 719;

  2. Gallea JI et al, J. Biol. Chem. 2014, 26733.

  3. Gallea JI et al, Biochim. Biophys. Acta. 2016, 501.

  4. Gallea JI et al, J. Neurochemistry. 2018, 541.

Localización : Aula Cardini
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Dra. M. Soledad Celej
Dto. de Química Biológica Ranwel Caputto
CIQUIBIC-CONICET
Facultad de Ciencias Químicas, Universidad Nacional de Córdoba.

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