Summary
RESEARCH INTERESTS
Our research focuses on the physical principles underlying functional processes of bio-macromolecules by using integrated approaches of biomolecular NMR experiments and multiscale molecular simulations. Our interests range from understanding protein dynamics and interactions to membrane proteins, intrinsically disordered proteins and supramolecular host-guest interactions.
Links: publications, citations, research highlights.
Recent Research Highlights
Mechanisms of misfolding of the Prion Protein. 
The misfolding and aggregation into amyloid fibrils of the prion protein (PrP) have been strongly linked with a group of neurodegenerative disorders that include the mad cow disease. Currently, the molecular origins of the prion diseases are unknown, including the underlying mechanisms of PrP misfolding and the regions promoting its aggregation. Here, we identified the structural basis by which the folded domain of the human PrP converts into amyloids. We showed that this process is promoted by intermediate species forming as a result of the pathological mutation T183A, and that POM antibodies are able to suppress completely the aggregation process by blocking the misfolding mechanism. This study thereby suggests possible molecular strategies to inhibit PrP aggregation into amyloids. See our recent PNAS article for more information.
The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition
α-Synuclein (αS) is a presynaptic disordered protein whose aberrant aggregation is associated with Parkinson's disease. Its functional role, however, is still debated. We have identified a structural mechanism by which αS stabilises the docking of synaptic vesicles with the plasma membrane, a process that might be relevant for the process of neurotransmitter release. More information is reported in our Nature Communication article.
Selected Publications
Journal Articles
Sanz-Hernandez M, Barritt JD, Sobek J, et al., 2021, Mechanism of misfolding of the human prion protein revealed by a pathological mutation, Proceedings of the National Academy of Sciences of the United States of America, Vol:118, ISSN:0027-8424
Man W, Tahirbegi B, Vrettas M, et al., 2021, The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition, Nature Communications, Vol:12, ISSN:2041-1723
Fusco G, Chen SW, Williamson PTF, et al., 2017, Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers, Science, Vol:358, ISSN:0036-8075, Pages:1440-1443
Fusco G, Pape T, Stephens AD, et al., 2016, Structural basis of synaptic vesicle assembly promoted by α-synuclein, Nature Communications, Vol:7, ISSN:2041-1723, Pages:1-12
Fusco G, De Simone A, Gopinath T, et al., 2014, Direct observation of the three regions in alpha-synuclein that determine its membrane-bound behaviour, Nature Communications, Vol:5, ISSN:2041-1723, Pages:1-8
Krieger JM, Fusco G, Lewitzky M, et al., 2014, Conformational Recognition of an Intrinsically Disordered Protein, Biophysical Journal, Vol:106, ISSN:0006-3495, Pages:1771-1779
Biedermann F, Uzunova VD, Scherman OA, et al., 2012, Release of High-Energy Water as an Essential Driving Force for the High-Affinity Binding of Cucurbit[n]urils, Journal of the American Chemical Society, Vol:134, ISSN:0002-7863, Pages:15318-15323