C-terminal truncation of α-synuclein alters DNA structure from extension to compaction
Journal article, 2021

Parkinson's disease (PD) is linked to aggregation of the protein α-synuclein (aS) into amyloid fibers. aS is proposed to regulate synaptic activity and may also play a role in gene regulation via interaction with DNA in the cell nucleus. Here, we address the role of the negatively-charged C-terminus in the interaction between aS and DNA using single-molecule techniques. Using nanofluidic channels, we demonstrate that truncation of the C-terminus of aS induces differential effects on DNA depending on the extent of the truncation. The DNA extension increases for full-length aS and the (1–119)aS variant, but decreases about 25% upon binding to the (1–97)aS variant. Atomic force microscopy imaging showed full protein coverage of the DNA at high aS concentration. The characterization of biophysical properties of DNA when in complex with aS variants may provide important insights into the role of such interactions in PD, especially since C-terminal aS truncations have been found in clinical samples from PD patients.

Atomic force microscopy

α-synuclein

DNA-protein binding

Single-molecule studies

Nanofluidic channel

Author

Kai Jiang

Chalmers, Biology and Biological Engineering, Chemical Biology

Sandra Rocha

Chalmers, Biology and Biological Engineering, Chemical Biology

Ranjeet Kumar

Chalmers, Biology and Biological Engineering, Chemical Biology

Fredrik Westerlund

Chalmers, Biology and Biological Engineering, Chemical Biology

Pernilla Wittung Stafshede

Chalmers, Biology and Biological Engineering, Chemical Biology

Biochemical and Biophysical Research Communications

0006-291X (ISSN) 1090-2104 (eISSN)

Vol. 568 43-47

Subject Categories

Biochemistry and Molecular Biology

Biophysics

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1016/j.bbrc.2021.06.059

More information

Latest update

7/22/2021