Unsaturated Fatty Acid-Induced Conformational Transitions and Aggregation of the Repeat Domain of Tau.
Molecules
; 25(11)2020 Jun 11.
Article
in En
| MEDLINE
| ID: mdl-32545360
ABSTRACT
BACKGROUND:
The intrinsically disordered, amyloidogenic protein Tau associates with diverse classes of molecules, including proteins, nucleic acids, and lipids. Mounting evidence suggests that fatty acid molecules could play a role in the dysfunction of this protein, however, their interaction with Tau remains poorly characterized.METHODS:
In a bid to elucidate the association of Tau with unsaturated fatty acids at the sub-molecular level, we carried out a variety of solution NMR experiments in combination with circular dichroism and fluorescence measurements. Our study shows that Tau4RD, the highly basic four-repeat domain of Tau, associates strongly with arachidonic and oleic acid assemblies in a high lipid/protein ratio, perturbing their supramolecular states and itself undergoing time-dependent structural adaptation. The structural signatures of Tau4RD/fatty acid aggregates appear similar for arachidonic acid and oleic acid, however, they are distinct from those of another prototypical intrinsically disordered protein, α-synuclein, when bound to these lipids, revealing protein-specific conformational adaptations. Both fatty acid molecules are found to invariably promote the self-aggregation of Tau4RD and of α-synuclein.CONCLUSIONS:
This study describes the reciprocal influence that Tau4RD and fatty acids exert on their conformational states, contributing to our understanding of fundamental aspects of Tau/lipid co-assembly.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arachidonic Acid
/
Tau Proteins
/
Oleic Acid
Limits:
Humans
Language:
En
Journal:
Molecules
Journal subject:
BIOLOGIA
Year:
2020
Type:
Article
Affiliation country:
Italy