| Autor: |
Mamchur AA; Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia., Moiseenko AV; Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia., Panina IS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia., Yaroshevich IA; Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia., Kudryavtseva SS; Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia., Pichkur EB; National Research Center, Kurchatov Institute, 123098 Moscow, Russia.; Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of NRC Kurchatov Institute, 188300 Gatchina, Russia., Sokolova OS; Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia., Muronetz VI; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia.; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia., Stanishneva-Konovalova TB; Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. |
| Abstrakt: |
The molecular chaperone GroEL is designed to promote protein folding and prevent aggregation. However, the interaction between GroEL and the prion protein, PrP C , could lead to pathogenic transformation of the latter to the aggregation-prone PrP Sc 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. |
