umu.sePublications
Change search
ReferencesLink to record
Permanent link

Direct link
Insulin-degrading enzyme is activated by the C-terminus of alpha-synuclein
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
2015 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 466, no 2, 192-195 p.Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
2015. Vol. 466, no 2, 192-195 p.
Keyword [en]
Insulin degrading enzyme, Parkinson's disease, alpha-Synuclein, Amyloid, Proteolysis
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:umu:diva-110991DOI: 10.1016/j.bbrc.2015.09.002ISI: 000362610800008PubMedID: 26343304OAI: oai:DiVA.org:umu-110991DiVA: diva2:872237
Available from: 2015-11-18 Created: 2015-11-02 Last updated: 2015-11-18Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Sharma, Sandeep K.Chorell, ErikWittung-Stafshede, Pernilla
By organisation
Department of Chemistry
In the same journal
Biochemical and Biophysical Research Communications - BBRC
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 65 hits
ReferencesLink to record
Permanent link

Direct link