Different Conformational Subensembles of the Intrinsically Disordered Protein α-Synuclein in Cells

The Journal of Physical Chemistry Letters
Mohammad A A FakhreeMireille M A E Claessens

Abstract

The intrinsically disordered protein α-synuclein (αS) is thought to play an important role in cellular membrane processes. Although in vitro experiments indicate that this initially disordered protein obtains structure upon membrane binding, NMR and EPR studies in cells could not single out any conformational subensemble. Here we microinjected small amounts of αS, labeled with a Förster resonance energy transfer (FRET) pair, into SH-SY5Y cells to investigate conformational changes upon membrane binding. Our FRET studies show a clear conformational difference between αS in the cytosol and when bound to small vesicles. The identification of these different conformational subensembles inside cells resolves the apparent contradiction between in vitro and in vivo experiments and shows that at least two different conformational subensembles of αS exist in cells. The existence of conformational subensembles supports the idea that αS can obtain different functions which can possibly be dynamically addressed with changing intracellular physicochemical conditions.

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Citations

Apr 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ersoy CholakBirthe B Kragelund
Mar 25, 2020·International Journal of Molecular Sciences·Arndt Wallmann, Christopher Kesten
Aug 26, 2018·International Journal of Molecular Sciences·Anna I SulatskayaKonstantin K Turoverov
Sep 20, 2019·Life Science Alliance·Justine LempartUrsula Jakob
Nov 16, 2019·NPJ Parkinson's Disease·Bryan A KillingerJeffrey H Kordower
Jan 23, 2021·Neuroscience·Mohammad A A FakhreeMireille M A E Claessens
Nov 2, 2019·Archives of Biochemistry and Biophysics·Mohammad A A FakhreeMireille M A E Claessens
Apr 12, 2019·Chemical Reviews·Ioana M Ilie, Amedeo Caflisch
Nov 14, 2019·Biomacromolecules·Matthias MarczynskiOliver Lieleg
Jan 18, 2019·Biomacromolecules·Mohammad A A FakhreeMireille M A E Claessens
Sep 18, 2021·Journal of Neurochemistry·Natasha S R BidesiMatthias M Herth
Nov 25, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Souvik MondalSanjoy Bandyopadhyay
Dec 4, 2021·ACS Chemical Neuroscience·Slav A SemerdzhievMireille M A E Claessens

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Methods Mentioned

BETA
NMR
Confocal microscopy
FRET
with

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