RECONSTITUTION OF HELICAL SOLUBLE -SYNUCLEIN THROUGH TRANSIENT INTERACTION WITH LIPID INTERFACES

-synuclein ( Syn) is one of the key players in the pathogenesis of Parkinsons disease (PD) and other synucleinopathies. Its misfolding and subsequent aggregation into intracellular inclusions are the pathological hallmark of these diseases and may also play a central role in the molecular cascade le...

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Bibliographic Details
Published inbioRxiv
Main Authors Rovere, Matteo, Sanderson, John B, Fonseca-Ornelas, Luis, Bartels, Tim
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 13.10.2017
Subjects
Chaperones
Interfaces
Lipid bilayers
Lipids
Movement disorders
Neurodegeneration
Neurodegenerative diseases
Oligomerization
Parkinson's disease
Synuclein
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Summary:-synuclein ( Syn) is one of the key players in the pathogenesis of Parkinsons disease (PD) and other synucleinopathies. Its misfolding and subsequent aggregation into intracellular inclusions are the pathological hallmark of these diseases and may also play a central role in the molecular cascade leading to neurodegeneration. In this work, we report the existence of a novel soluble -helical conformer of Syn, an archetypal intrinsically disordered protein (IDP), obtained through transient interaction with lipid interfaces. We describe how the stability of this conformer is highly dependent on the continuous, dynamic oligomerization of the folded species. The conformational space of Syn appears to be highly context-dependent, and lipid bilayers might play crucial roles as molecular chaperones for cytosolic species in a cellular environment, as they do in the case of this previously unreported structure.
DOI:10.1101/202994