Pro-Inflammatory S100A9 Protein Aggregation Promoted by NCAM1 Peptide Constructs

Jonathan Pansieri, Lucija Ostojić, Igor A. Iashchishyn, Mazin Magzoub, Cecilia Wallin, Sebastian K.T.S. Wärmländer, Astrid Gräslund, Mai Nguyen Ngoc, Vytautas Smirnovas, Željko Svedružić, Ludmilla A. Morozova-Roche

Research output: Contribution to journalArticlepeer-review

Abstract

Amyloid cascade and neuroinflammation are hallmarks of neurodegenerative diseases, and pro-inflammatory S100A9 protein is central to both of them. Here, we have shown that NCAM1 peptide constructs carrying polycationic sequences derived from Aβ peptide (KKLVFF) and PrP protein (KKRPKP) significantly promote the S100A9 amyloid self-assembly in a concentration-dependent manner by making transient interactions with individual S100A9 molecules, perturbing its native structure and acting as catalysts. Since the individual molecule misfolding is a rate-limiting step in S100A9 amyloid aggregation, the effects of the NCAM1 construct on the native S100A9 are so critical for its amyloid self-assembly. S100A9 rapid self-assembly into large aggregated clumps may prevent its amyloid tissue propagation, and by modulating S100A9 aggregation as a part of the amyloid cascade, the whole process may be effectively tuned.

Original languageEnglish (US)
Pages (from-to)1410-1417
Number of pages8
JournalACS Chemical Biology
Volume14
Issue number7
DOIs
StatePublished - Jul 19 2019

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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