Molecular details of α-synuclein membrane association revealed by neutrons and photons

The Journal of Physical Chemistry. B
Zhiping JiangJennifer C Lee

Abstract

α-Synuclein (α-syn) is an abundant neuronal protein associated with Parkinson's disease that is disordered in solution, but it exists in equilibrium between a bent-helix and an elongated-helix on negatively charged membranes. Here, neutron reflectometry (NR) and fluorescence spectroscopy were employed to uncover molecular details of the interaction between α-syn and two anionic lipids, phosphatidic acid (PA) and phosphatidylserine (PS). Both NR and site-specific Trp measurements indicate that penetration depth of α-syn is similar for either PA- or PS-containing membranes (∼9-11 Å from bilayer center) even though there is a preference for α-syn binding to PA. However, closer examination of the individual Trp quenching profiles by brominated lipids reveals differences into local membrane interactions especially at position 39 where conformational heterogeneity was observed. The data also indicate that while W94 penetrates the bilayer as deeply as W4, W94 resides in a more polar surrounding. Taken together, we suggest the N- and C-terminal regions near positions 4 and 94 are anchored to the membrane, while the putative linker spanning residue 39 samples multiple conformations, which are sensitive to the chemical nature of the memb...Continue Reading

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Citations

Mar 15, 2016·Biochimica Et Biophysica Acta·A WestJ N Sachs
Mar 5, 2016·Biochimica Et Biophysica Acta·Javier L BaylonEmad Tajkhorshid
Dec 10, 2016·The Journal of Physical Chemistry Letters·Zhiping JiangJennifer C Lee
May 5, 2017·The Journal of Physical Chemistry Letters·Jessica D Flynn, Jennifer C Lee
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May 3, 2019·The Journal of Biological Chemistry·Matteo RovereTim Bartels
Aug 18, 2016·The Journal of Biological Chemistry·Aditya IyerVinod Subramaniam
Nov 26, 2019·Journal of Computational Chemistry·Shashank Pant, Emad Tajkhorshid
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Jul 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Upneet Kaur, Jennifer C Lee
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Apr 10, 2021·The Journal of Physical Chemistry. B·Sydney O Shuster, Jennifer C Lee
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Oct 27, 2017·Journal of the American Chemical Society·Arnaldo L SerranoMartin T Zanni
Sep 11, 2021·ACS Chemical Neuroscience·Altmash KhanRadhakrishnan Mahalakshmi

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