조규성 (Ku-Sung Jo) 건국대학교
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J. Mol. Biol., Volume 431, Issue 7, 29 March 2019, Pages 1468-1480 | https://doi.org/10.1016/j.jmb.2019.02.022
Unique Unfoldase/Aggregase Activity of a Molecular Chaperone Hsp33 in its Holding-Inactive State
펼치기 Authors and Affiliations
Abstract

The various chaperone activities of heat shock proteins contribute to ensuring cellular proteostasis. Here, we demonstrate the non-canonical unfoldase activity as an inherent functionality of the prokaryotic molecular chaperone, Hsp33. Hsp33 was originally identified as a holding chaperone that is post-translationally activated by oxidation. However, in this study, we verified that the holding-inactive reduced form of Hsp33 (RHsp33) strongly bound to the translational elongation factor, EF-Tu. This interaction was critically mediated by the redox-switch domain of RHsp33 and the guanine nucleotide-binding domain of EF-Tu. The bound RHsp33, without undergoing any conformational change, catalyzed the EF-Tu aggregation by evoking the aberrant folding of EF-Tu to expose hydrophobic surfaces. Consequently, the oligomers/aggregates of EF-Tu, but not its functional monomeric form, were highly susceptible to proteolytic degradation by Lon protease. These findings present a unique example of an ATP-independent molecular chaperone with distinctive dual functions—as an unfoldase/aggregase and as a holding chaperone—depending on the redox status. It is also suggested that the unusual unfoldase/aggregase activity of RHsp33 can contribute to cellular proteostasis by dysregulating EF-Tu under heat-stressed conditions.

Abbreviations
ANS, 8-anilino-1-naphthalene sulfonic acid; CD, circular dichroism; D2, domain-II; D3, domain-III; DTT, dithiothreitol; EDTA, ethylenediaminetetraacetic acid; EF-Ts, elongation factor thermal-stable; EF-Tu, elongation factor thermal-unstable; GD, guanidine nucleotide-binding domain; Hsp33, heat shock protein 33; ITC, isothermal titration calorimetry; MLD, middle linker domain; RSD, redox-switch domain; TROSY, transverse relaxation optimized spectroscopy

Keywords : proteostasis; protein quality control; protein turnover; protein misfolding; protein aggregation

Category: Biochemistry, Molecular_Biology
추천자 : Faculty of 1000 Biology
Collet J and Goemans C: F1000Prime Recommendation of [Jo KS et al., J Mol Biol 2019 431(7):1468-1480]. In F1000Prime, 18 Sep 2019; 10.3410/f.735222321.793565263
등록일 2019.09.20
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