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?-Synuclein suppresses both the initiation and amplification steps of ?-synuclein aggregation via competitive binding to surfaces.


ABSTRACT: ?-Synuclein is an intrinsically disordered protein that is associated with the pathogenesis of Parkinson's disease through the processes involved in the formation of amyloid fibrils. ? and ?-synuclein are homologous proteins found at comparable levels in presynaptic terminals but ?-synuclein has a greatly reduced propensity to aggregate and indeed has been found to inhibit ?-synuclein aggregation. In this paper, we describe how sequence differences between ?- and ?-synuclein affect individual microscopic processes in amyloid formation. In particular, we show that ?-synuclein strongly suppresses both lipid-induced aggregation and secondary nucleation of ?-synuclein by competing for binding sites at the surfaces of lipid vesicles and fibrils, respectively. These results suggest that ?-synuclein can act as a natural inhibitor of ?-synuclein aggregation by reducing both the initiation of its self-assembly and the proliferation of its aggregates.

SUBMITTER: Brown JW 

PROVIDER: S-EPMC5093550 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces.

Brown James W P JW   Buell Alexander K AK   Michaels Thomas C T TC   Meisl Georg G   Carozza Jacqueline J   Flagmeier Patrick P   Vendruscolo Michele M   Knowles Tuomas P J TP   Dobson Christopher M CM   Galvagnion Céline C  

Scientific reports 20161103


α-Synuclein is an intrinsically disordered protein that is associated with the pathogenesis of Parkinson's disease through the processes involved in the formation of amyloid fibrils. α and β-synuclein are homologous proteins found at comparable levels in presynaptic terminals but β-synuclein has a greatly reduced propensity to aggregate and indeed has been found to inhibit α-synuclein aggregation. In this paper, we describe how sequence differences between α- and β-synuclein affect individual mi  ...[more]

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