The amyloidogenic properties of the CAP superfamily proteins

Abstract

Functional protein aggregation is observed in several proteins, serving diverse purposes in numerous biological processes, and is regulated by complex mechanisms. To avoid potential toxicity of intermediates during protein self-association, functional protein aggregation undergoes fast growth rate to minimize the generation of detrimental oligomers. Moreover, a variety of functional protein aggregates are reversibly regulated, which indicates a highly dynamic process of efficient ways to rapidly and specifically organize protein assemblies in response to cellular changes. In this thesis, we discussed the role of multiple biomolecular factors, such as lipids, GAGs, nuclei acids, polyP, metal ions, PTMs, HSPs, proteases and polyphenols, in regulating physiological and/or reversible protein aggregates. Diverse factors affect GAPR-1 aggregation, which is proposed to be associated with its functions in autophagy, immunology and reproduction. Moreover, by using GAPR-1 as a model protein of CAP superfamily members, we suggest that oligomerization could be a common property of the CAP superfamily. Self-association and/or disaggregation could be a general mechanism in modulating functions of CAP family members, providing new clues on a molecular understanding of these and other functional aggregates as well as potential clues for treatment and prevention of protein aggregation-related diseases.