Alpha-Synuclein Modulates the Physical Properties of DNA

Kai Jiang, Sandra Rocha, Alvina Westling, Sriram Kesarimangalam, Kevin D. Dorfman, Pernilla Wittung-Stafshede, Fredrik Westerlund

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Fundamental research on Parkinson's disease (PD) most often focuses on the ability of α-synuclein (aS) to form oligomers and amyloids, and how such species promote brain cell death. However, there are indications that aS also plays a gene-regulatory role in the cell nucleus. Here, the interaction between monomeric aS and DNA in vitro has been investigated with single-molecule techniques. Using a nanofluidic channel system, it was discovered that aS binds to DNA and by studying the DNA–protein complexes at different confinements we determined that aS binding increases the persistence length of DNA from 70 to 90 nm at high coverage. By atomic force microscopy it was revealed that at low protein-to-DNA ratio, the aS binding occurs as small protein clusters scattered along the DNA; at high protein-to-DNA ratio, the DNA is fully covered by protein. As DNA-aS interactions may play roles in PD, it is of importance to characterize biophysical properties of such complexes in detail.

Original languageEnglish (US)
Pages (from-to)15685-15690
Number of pages6
JournalChemistry - A European Journal
Volume24
Issue number58
DOIs
StatePublished - Oct 17 2018

Bibliographical note

Funding Information:
Kai Jiang holds a personal grant from the Wenner-Gren Foundation. PWS and FW both acknowledge funding from the Olle Engqvist Foundation and the Swedish Research Council (PWS no 2015-3881, FW no. 2015-5062), and KDD acknowledges funding from the National Institutes of Health (R01-HG006851). PWS also acknowledges funding from the Knut and Alice Wal-lenberg Foundation. We thank Ranjeet Kumar (Chalmers) for help with protein production and Yii-Lih Lin (Chalmers) for the software for analyzing the nanochannel data.

Keywords

  • DNA
  • biochemistry
  • nanofluidics
  • proteins
  • synuclein

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