C-terminal truncation of α-synuclein alters DNA structure from extension to compaction.

Abstract

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.

• Authors: Kai Jiang, Sandra Rocha, Ranjeet Kumar, Fredrik Westerlund, Pernilla Wittung-Stafshede
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 568 Pg. 43-47 (09 03 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 34175689 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• alpha-Synuclein
• DNA

Topics

• Amino Acid Sequence
• DNA (chemistry, metabolism)
• Humans
• Nucleic Acid Conformation
• Parkinson Disease (metabolism)
• Protein Aggregation, Pathological (metabolism)
• Protein Domains
• alpha-Synuclein (chemistry, metabolism)