Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 13, Issue 3, Pages 2893-2917Publisher
MDPI
DOI: 10.3390/ijms13032893
Keywords
S100A8; S100A9; S100 proteins; amyloid; inflammation; cancer; self-assembly; calcium-binding; calprotectin
Funding
- Swedish Medical Research Council
- Insamlingsstiftelsen Umea and Biochemical Imaging Centre Umea
Ask authors/readers for more resources
S100A8 and S100A9 are EF-hand Ca2+ binding proteins belonging to the S100 family. They are abundant in cytosol of phagocytes and play critical roles in numerous cellular processes such as motility and danger signaling by interacting and modulating the activity of target proteins. S100A8 and S100A9 expression levels increased in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases and they are implicated in the numerous disease pathologies. The Ca2+ and Zn2+-binding properties of S100A8/A9 have a pivotal influence on their conformation and oligomerization state, including self-assembly into homo- and heterodimers, tetramers and larger oligomers. Here we review how the unique chemical and conformational properties of individual proteins and their structural plasticity at the quaternary level account for S100A8/A9 functional diversity. Additional functional diversification occurs via non-covalent assembly into oligomeric and fibrillar amyloid complexes discovered in the aging prostate and reproduced in vitro. This process is also regulated by Ca2+ and Zn2+-binding and effectively competes with the formation of the native complexes. High intrinsic amyloid-forming capacity of S100A8/A9 proteins may lead to their amyloid depositions in numerous ailments characterized by their elevated expression patterns and have additional pathological significance requiring further thorough investigation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available