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ACS Chem Biol. 2019 Jul 19;14(7):1410-1417. doi: 10.1021/acschembio.9b00394. Epub 2019 Jun 13.

Pro-Inflammatory S100A9 Protein Aggregation Promoted by NCAM1 Peptide Constructs.

Author information

1
Department of Medical Biochemistry and Biophysics , Umeå University , SE-901 87 Umeå , Sweden.
2
New York University Abu Dhabi , Saadiyat Island, Abu Dhabi , United Arab Emirates.
3
Department of Biochemistry and Biophysics, Arrhenius Laboratories , Stockholm University , Stockholm , Sweden.
4
Institute of Biotechnology, Life Sciences Center , Vilnius University , Vilnius , Lithuania.
5
Department of Biomedical Technology , University of Rijeka , HR 51000 , Rijeka , Croatia.

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.

PMID:
31194501
DOI:
10.1021/acschembio.9b00394

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