Year-end Sale % OFF 
Abstract
Human cystatin C (hCC), a member of the superfamily of papain-like cysteine protease inhibitors, is the most widespread cystatin in human body fluids. Physiologically active hCC is a monomer, which dimerization and oligomerization lead to the formation of the inactive, insoluble amyloid form of the protein, strictly associated with cerebral amyloid angiopathy, a severe state causing death among young patients. It is known, that biological membranes may accelerate the oligomerization processes of amyloidogenic proteins. Therefore, in this study, we describe an influence of membrane mimetic environment—mixed dodecylphosphocholine:sodium dodecyl sulfate (DPC:SDS) micelle (molar ratio 5:1)—on the effect of the hCC oligomerization. The hCC–micelle interactions were analyzed with size exclusion chromatography, circular dichroism, and nuclear magnetic resonance spectroscopy. The experiments were performed on the wild-type (WT) cystatin C, and two hCC variants—V57P and V57G. Collected experimental data were supplemented with molecular dynamic simulations, making it possible to highlight the binding interface and select the residues involved in interactions with the micelle. Obtained data shows that the mixed DPC:SDS micelle does not accelerate the oligomerization of protein and even reverses the hCC dimerization process.
Highlights
An amyloid is a name used for the description of a specific state of a protein in which its molecules are self-assembled into an insoluble form featuring a characteristic fiber-like structure
For the purpose of this study, the Human cystatin C (hCC) variants were selected depending on their distinct properties in comparison to the wild-type (WT) protein, which, in physiological conditions, occurs in a monomeric form [29]
The hCC analogs with a mutation in position 57 were selected, since the valine (V57) is the most highly conserved residue in the structures of the whole cystatin family [30] and has a strained conformation what may be important for the biological activity of the protein [29]
Summary
An amyloid is a name used for the description of a specific state of a protein (or peptide) in which its molecules are self-assembled (aggregated) into an insoluble form featuring a characteristic fiber-like structure. The diseases involving amyloid formation are generally called amyloidoses [3]. They include i.a. rheumatoid arthritis and Alzheimer’s, Parkinson’s, or Creutzfeldt–Jakob diseases [4,5]. The problem is especially visible in the case of a subtype of amyloidoses affecting the central nervous system, where the mental impairment caused by the disease results in the need for constant medical attention and supervision over the patient who, in an advanced stage of the disease, cannot cope even with simple everyday actions. A lot of effort is being focused on the studies related to the detailed description of protein oligomerization processes and possible factors and routes which could prevent them
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
