한빛사 논문
Ku-Sung Jo1,†, Ji-Hun Kim2, Kyoung-Seok Ryu3, Joo-Seong Kang1, Chae-Yeon Wang1, Yoo-Sup Lee1,4,5, Min-Duk Seo4, Young-Ho Lee3, Hyung-Sik Won1,*
1 Department of Biotechnology, Research Institute (RIBHS) and College of Biomedical & Health Science, Konkuk University, Chungju, Chungbuk 27478, Republic of Korea
2 College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea
3 Protein Structure Group, Korea Basic Science Institute, Ochang, Chungbuk 28199, Republic of Korea
4 College of Pharmacy and Department of Molecular Science and Technology, Ajou University, Suwon, Gyeonggi 16499, Republic of Korea
5 Present address: Y.-S. Lee, Analytics Team, R&D Division, POLUS Inc., Incheon 21984, Republic of Korea.
† K.-S. Jo was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant no. G201809G00019).
*Corresponding author : Hyung-Sik Won
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
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기