Insulin-degrading enzyme is activated by the C-terminus of α-synuclein.
Artikel i vetenskaplig tidskrift, 2015

The insulin-degrading enzyme (IDE) plays a key role in type-2 diabetes and typically degrades small peptides such as insulin, amyloid β and islet amyloid polypeptide. We recently reported a novel non-proteolytical interaction in vitro between IDE and the Parkinson's disease 140-residue protein α-synuclein that resulted in dual effects: arrested α-synuclein oligomers and, simultaneously, increased IDE proteolysis activity. Here we demonstrate that these outcomes arise due to IDE interactions with the C-terminus of α-synuclein. Whereas a peptide containing the first 97 residues of α-synuclein did not improve IDE activity and its aggregation was not blocked by IDE, a peptide with the C-terminal 44 residues of α-synuclein increased IDE proteolysis to the same degree as full-length α-synuclein. Because the α-synuclein C-terminus is acidic, the interaction appears to involve electrostatic attraction with IDE's basic exosite, known to be involved in activation.

metabolism

chemistry

Microscopy

alpha-Synuclein

Insulysin

Atomic Force

Enzyme Activation

metabolism

Författare

Sandeep K Sharma

E. Chorell

Pernilla Wittung Stafshede

Chalmers, Biologi och bioteknik, Kemisk biologi

Biochemical and Biophysical Research Communications

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

Vol. 466 192-5

Ämneskategorier

Biologiska vetenskaper

Biofysik

DOI

10.1016/j.bbrc.2015.09.002

PubMed

26343304