Taking Charge: Metal Ions Accelerate Amyloid Aggregation in Sequence Variants of α-Synuclein.

ABSTRACT: Αlpha-synuclein (αS) is an intrinsically disordered protein which exhibits a high degree of conformational heterogeneity. In vivo, αS experiences various environments which cause adaptation of its structural ensemble. Divalent metal ions are prominent in synaptic terminals where αS is located and are thought to bind to the αS C-terminal region. Herein, we used native nanoelectrospray ionization ion mobility-mass spectrometry to investigate changes in the charge state distribution and collision cross sections of wild-type N-terminally acetylated (NTA) αS, along with a deletion variant (ΔΔNTA) which inhibits amyloid formation and a C-terminal truncated variant (119NTA) which increases the rate of amyloid formation. We also examine the effect of the addition of divalent metal ions, Ca<

SUBMITTER: Byrd EJ 

PROVIDER: S-EPMC9983014 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature