Monitoring the interactions between POPG phospholipid bilayer and amyloid-forming protein human cystatin C. Does the bilayer influence the oligomeric state and structure of the protein?

A biological membrane is a structure characteristic for various cells and organelles present in almost all living organisms. Even though, it is one of the most common structures in organisms, where it serves crucial functions, a phospholipid bilayer may also take part in pathological processes leading to severe diseases. Research indicates that biological membranes have a profound impact on the pathological processes of oligomerization of amyloid-forming proteins. These processes are a hallmark of amyloid diseases, a group of pathological states involving, e.g., Parkinson's or Alzheimer's disease. Even though amyloidogenic diseases reap the harvest in modern societies, especially in elderly patients, the mechanisms governing the amyloid deposition are not clearly described. Therefore, the presented study focuses on the description of interactions between a model biological membrane (POPG) and one of amyloid forming proteins - human cystatin C. For the purpose of the study molecular dynamics simulations were applied to confirm interactions between the protein and POPG membrane. Next the NMR techniques were used to verify how the data obtained in solution compared to MD simulations and determine fragments of the protein responsible for interactions with POPG. Finally, circular dichroism was used to monitor the changes in secondary structure of the protein and size exclusion chromatography was used to monitor its oligomerization process. Obtained data indicates that the protein interacts with POPG submerging itself into the bilayer with the AS region. However, the presence of POPG bilayer does not significantly affect the structure or oligomerization process of human cystatin C.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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