Structural and Computational Study of the GroEL–Prion Protein Complex

Mamchur, Aleksandra A.; Moiseenko, Andrei V.; Panina, Irina; Yaroshevich, Igor A.; Kudryavtseva, Sofia S.; Pichkur, Evgeny; Sokolova, Olga; Muronetz, Vladimir I.

doi:10.3390/biomedicines9111649

Cited by 7 publications

(8 citation statements)

References 38 publications

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“…Molecular dynamics was carried out at neutral pH using the GROMACS package [ 45 ] version 2020.1 and the a99SB-disp force field [ 46 ], which is used to model both structured and unstructured proteins [ 47 ]. An integration time step of 2 fs was used, and three-dimensional periodic boundary conditions were imposed.…”

Section: Methodsmentioning

confidence: 99%

Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

et al. 2022

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Variants of SARS-CoV-2 keep emerging and causing new waves of COVID-19 around the world. Effective new approaches in drug development are based on the binding of agents, such as neutralizing monoclonal antibodies to a receptor-binding domain (RBD) of SARS-CoV-2 spike protein. However, mutations in RBD may lower the affinity of previously developed antibodies. Therefore, rapid analysis of new variants and selection of a binding partner with high affinity is of great therapeutic importance. Here, we explore a computational approach based on molecular dynamics simulations and conformational clusterization techniques for the wild-type and omicron variants of RBD. Biochemical experiments support the hypothesis of the presence of several conformational states within the RBD assembly. The development of such an approach will facilitate the selection of neutralization drugs with higher affinity based on the primary structure of the target antigen.

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Section: Methodsmentioning

confidence: 99%

Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

et al. 2022

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“…Recent studies including the works of our group have visualized the interaction of monomers of a prion protein cellular isoform with the bacterial chaperonin GroEL ( Figure 1 ) [ 85 ]. This interaction with GroEL in the absence of GroES leads to the amyloid transformation of PrPc, resulting in the formation of large amyloid aggregates [ 57 ].…”

Section: Influence Of Chaperones On Pathological Transformation Of Am...mentioning

confidence: 99%

“…Thus, it was shown that prion protein monomers bind in the internal cavity of the GroEL chaperonin. Such binding decreases the flexibility of the chaperonin ring in which the prion protein is bound [ 85 ]. The interaction of PrPc with GroEL disturbs the functioning of the GroEL–GroES complex: the chaperonin loses its ability to reactivate denatured GAPDH [ 86 ].…”

Section: Blocking Of Chaperones By Misfolded Proteins and Amyloidogen...mentioning

confidence: 99%

Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases

Muronetz

Kudryavtseva

Leisi

et al. 2022

IJMS

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The review highlights various aspects of the influence of chaperones on amyloid proteins associated with the development of neurodegenerative diseases and includes studies conducted in our laboratory. Different sections of the article are devoted to the role of chaperones in the pathological transformation of alpha-synuclein and the prion protein. Information about the interaction of the chaperonins GroE and TRiC as well as polymer-based artificial chaperones with amyloidogenic proteins is summarized. Particular attention is paid to the effect of blocking chaperones by misfolded and amyloidogenic proteins. It was noted that the accumulation of functionally inactive chaperones blocked by misfolded proteins might cause the formation of amyloid aggregates and prevent the disassembly of fibrillar structures. Moreover, the blocking of chaperones by various forms of amyloid proteins might lead to pathological changes in the vital activity of cells due to the impaired folding of newly synthesized proteins and their subsequent processing. The final section of the article discusses both the little data on the role of gut microbiota in the propagation of synucleinopathies and prion diseases and the possible involvement of the bacterial chaperone GroE in these processes.

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“…Structural studies of different substrates bound to nucleotide-free GroEL have been published, including malate dehydrogenase (9), gp23 (10), PepQ (11), Rubisco (12), actin (13), and PrP (14). Together, these studies show that non-native proteins initially bind multivalently and in different configurations to GroEL apical domains, allowing GroEL to capture structurally distinct folding intermediates.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of substrate progression through the chaperonin cycle

Gardner

Darrow

Lukoyanova

et al. 2023

Preprint

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The bacterial chaperonin GroEL-GroES promotes protein folding through ATP-regulated cycles of substrate protein binding, encapsulation, and release. Here, we have used cryoEM to determine structures of GroEL, GroEL-ADP.BeF3, and GroEL-ADP.AlF3-GroES all complexed with the model substrate Rubisco. Our structures provide a series of snapshots that show how the conformation and interactions of non-native Rubisco change as it proceeds through the GroEL-GroES reaction cycle. We observe specific charged and hydrophobic GroEL residues forming strong initial contacts with non-native Rubisco. Binding of ATP or ADP.BeF3 to GroEL-Rubisco results in the formation of an intermediate GroEL complex displaying striking asymmetry in the ATP/ADP.BeF3-bound ring. In this ring, four GroEL subunits bind Rubisco and the other three are in the GroES-accepting conformation, explaining how GroEL can recruit GroES without releasing bound substrate. Our cryoEM structures of stalled GroEL-ADP.AlF3-Rubisco-GroES complexes show Rubisco folding intermediates interacting with GroEL-GroES via different sets of residues.

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Structural and Computational Study of the GroEL–Prion Protein Complex

Cited by 7 publications

References 38 publications

Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases

Structural basis of substrate progression through the chaperonin cycle

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