Imperial College London
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ProfessorAlfonsoDe Simone

Faculty of Natural Sciences, Department of Life Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3052a.de-simon Website

 
 
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Location

 

603Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fusco:2016:10.1038/ncomms12563,
author = {Fusco, G and Pape, T and Stephens, AD and Mahou, P and Costa, A and Kaminski, CF and Kaminski-Schierle, GF and Vendruscolo, M and Veglia, G and Dobson, CM and De, Simone A},
doi = {10.1038/ncomms12563},
journal = {Nature Communications},
pages = {1--12},
title = {Structural basis of synaptic vesicle assembly promoted by α-synuclein},
url = {http://dx.doi.org/10.1038/ncomms12563},
volume = {7},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - α-synuclein (αS) is an intrinsically disordered protein whose fibrillar aggregates are the major constituents of Lewy bodies in Parkinson’s disease. 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. Here we report the analysis of wild-type αS and two mutational variants linked to familial Parkinson’s disease to describe the structural basis of a molecular mechanism enabling αS to induce the clustering of synaptic vesicles. We provide support for this ‘double-anchor’ mechanism by rationally designing and experimentally testing a further mutational variant of αS engineered to promote stronger interactions between synaptic vesicles. Our results characterize the nature of the active conformations of αS that mediate the clustering of synaptic vesicles, and indicate their relevance in both functional and pathological contexts.
AU  - Fusco,G
AU  - Pape,T
AU  - Stephens,AD
AU  - Mahou,P
AU  - Costa,A
AU  - Kaminski,CF
AU  - Kaminski-Schierle,GF
AU  - Vendruscolo,M
AU  - Veglia,G
AU  - Dobson,CM
AU  - De,Simone A
DO  - 10.1038/ncomms12563
EP  - 12
PY  - 2016///
SN  - 2041-1723
SP  - 1
TI  - Structural basis of synaptic vesicle assembly promoted by α-synuclein
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms12563
UR  - https://www.nature.com/articles/ncomms12563
UR  - http://hdl.handle.net/10044/1/37104
VL  - 7
ER  -
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