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.
De Simone Lab (Dec 2017)
Recent Research Highlights
Mechanism of membrane disruption and neuronal toxicity by Alpha-Synuclein oligomers.
α-synuclein (αS) is an intrinsically disordered protein whose fibrillar aggregates are the major constituents of Lewy bodies in Parkinson’s disease. Our recent research has addressed the structural properties of toxic αS oligomers and the molecular basis by which these aggregates induce neuronal toxicity. More details on our Science paper.
Structural Mechanism of Synaptic Vesicle Assembly by Alpha-Synuclein
Although the specific function of αS is still unclear, a general consensus is forming that it has a key role in regulating the process of neurotransmitter release, which is associated with the mediation of synaptic vesicle interactions and assembly. We characterised the structural mechanism enabling αS to induce the clustering of synaptic vesicles. More details can be found on our Nature Communication article.
et al., 2017, Structural basis of membrane disruption and cellular toxicity by alpha-synuclein oligomers, Science, Vol:358, ISSN:0036-8075, Pages:1440-+
et al., 2016, Structural basis of synaptic vesicle assembly promoted by alpha-synuclein, Nature Communications, Vol:7, ISSN:2041-1723
et al., 2016, Accurate Determination of Conformational Transitions in Oligomeric Membrane Proteins, Scientific Reports, Vol:6, ISSN:2045-2322
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
et al., 2014, Conformational Recognition of an Intrinsically Disordered Protein, Biophysical Journal, Vol:106, ISSN:0006-3495, Pages:1771-1779
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
et al., 2012, Intrinsic disorder modulates protein self-assembly and aggregation, Proceedings of the National Academy of Sciences of the United States of America, Vol:109, ISSN:0027-8424, Pages:6951-6956