Open AccessThis article is
- freely available
Pro-Inflammatory S100A8 and S100A9 Proteins: Self-Assembly into Multifunctional Native and Amyloid Complexes
Institute of Immunology, University of Muenster, Röntgenstr. 21, 48149 Muenster, Germany
Department of Medical Biochemistry and Biophysics, Umea University, SE-901 87 Umea, Sweden
* Author to whom correspondence should be addressed.
Received: 9 January 2012; in revised form: 21 February 2012 / Accepted: 22 February 2012 / Published: 5 March 2012
Abstract: 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.
Keywords: S100A8; S100A9; S100 proteins; amyloid; inflammation; cancer; self-assembly; calcium-binding; calprotectin
Article StatisticsClick here to load and display the download statistics.
Notes: Multiple requests from the same IP address are counted as one view.
Cite This Article
MDPI and ACS Style
Vogl, T.; Gharibyan, A.L.; Morozova-Roche, L.A. Pro-Inflammatory S100A8 and S100A9 Proteins: Self-Assembly into Multifunctional Native and Amyloid Complexes. Int. J. Mol. Sci. 2012, 13, 2893-2917.
Vogl T, Gharibyan AL, Morozova-Roche LA. Pro-Inflammatory S100A8 and S100A9 Proteins: Self-Assembly into Multifunctional Native and Amyloid Complexes. International Journal of Molecular Sciences. 2012; 13(3):2893-2917.
Vogl, Thomas; Gharibyan, Anna L.; Morozova-Roche, Ludmilla A. 2012. "Pro-Inflammatory S100A8 and S100A9 Proteins: Self-Assembly into Multifunctional Native and Amyloid Complexes." Int. J. Mol. Sci. 13, no. 3: 2893-2917.