Structural and Computational Study of the GroEL–Prion Protein Complex

The molecular chaperone GroEL is designed to promote protein folding and prevent aggregation. However, the interaction between GroEL and the prion protein, PrPC, could lead to pathogenic transformation of the latter to the aggregation-prone PrPSc form. Here, the molecular basis of the interactions i...

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Bibliographic Details
Published in:Biomedicines 2021-11, Vol.9 (11), p.1649
Main Authors: Mamchur, Aleksandra A., Moiseenko, Andrei V., Panina, Irina S., Yaroshevich, Igor A., Kudryavtseva, Sofia S., Pichkur, Evgeny B., Sokolova, Olga S., Muronetz, Vladimir I., Stanishneva-Konovalova, Tatiana B.
Format: Article
Language:English
Subjects:
Amino acids
Computer applications
Cryo-EM
Disease
GroEL
molecular chaperones
molecular dynamics
Nucleotides
Peptides
Prion protein
Protein folding
Proteins
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Summary:The molecular chaperone GroEL is designed to promote protein folding and prevent aggregation. However, the interaction between GroEL and the prion protein, PrPC, could lead to pathogenic transformation of the latter to the aggregation-prone PrPSc form. Here, the molecular basis of the interactions in the GroEL–PrP complex is studied with cryo-EM and molecular dynamics approaches. The obtained cryo-EM structure shows PrP to be bound to several subunits of GroEL at the level of their apical domains. According to MD simulations, the disordered N-domain of PrP forms much more intermolecular contacts with GroEL. Upon binding to the GroEL, the N-domain of PrP begins to form short helices, while the C-domain of PrP exhibits a tendency to unfold its α2-helix. In the absence of the nucleotides in the system, these processes are manifested at the hundred nanoseconds to microsecond timescale.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9111649