How soluble misfolded proteins bypass chaperones at the molecular level

Ritaban Halder, Daniel A. Nissley, Ian Sitarik, Yang Jiang, Yiyun Rao, Quyen V. Vu, Mai Suan Li, Justin Pritchard and Edward P. O’Brien ()
Additional contact information
Ritaban Halder: Pennsylvania State University
Daniel A. Nissley: Pennsylvania State University
Ian Sitarik: Pennsylvania State University
Yang Jiang: Pennsylvania State University
Yiyun Rao: Pennsylvania State University
Quyen V. Vu: Polish Academy of Sciences; Al. Lotnikow 32/46
Mai Suan Li: Polish Academy of Sciences; Al. Lotnikow 32/46
Justin Pritchard: Pennsylvania State University
Edward P. O’Brien: Pennsylvania State University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Subpopulations of soluble, misfolded proteins can bypass chaperones within cells. The extent of this phenomenon and how it happens at the molecular level are unknown. Through a meta-analysis of the experimental literature we find that in all quantitative protein refolding studies there is always a subpopulation of soluble but misfolded protein that does not fold in the presence of one or more chaperones, and can take days or longer to do so. Thus, some misfolded subpopulations commonly bypass chaperones. Using multi-scale simulation models we observe that the misfolded structures that bypass various chaperones can do so because their structures are highly native like, leading to a situation where chaperones do not distinguish between the folded and near-native-misfolded states. More broadly, these results provide a mechanism by which long-time scale changes in protein structure and function can persist in cells because some misfolded states can bypass components of the proteostasis machinery.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38962-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38962-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38962-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().