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Unique Unfoldase/Aggregase Activity of a Molecular Chaperone Hsp33 in its Holding-Inactive State
Jo, Ku-Sung,Kim, Ji-Hun,Ryu, Kyoung-Seok,Kang, Joo-Seong,Wang, Chae-Yeon,Lee, Yoo-Sup,Seo, Min-Duk,Lee, Young-Ho,Won, Hyung-Sik Academic Press 2019 Journal of molecular biology Vol.431 No.7
<P><B>Abstract</B></P> <P>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 (<SUP>R</SUP>Hsp33) strongly bound to the translational elongation factor, EF-Tu. This interaction was critically mediated by the redox-switch domain of <SUP>R</SUP>Hsp33 and the guanine nucleotide-binding domain of EF-Tu. The bound <SUP>R</SUP>Hsp33, 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 <SUP>R</SUP>Hsp33 can contribute to cellular proteostasis by dysregulating EF-Tu under heat-stressed conditions.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Hsp33 was originally identified as an oxidation-dependent holding chaperone. </LI> <LI> Holding-inactive reduced form of Hsp33 (<SUP>R</SUP>Hsp33) specifically interacted with EF-Tu. </LI> <LI> <SUP>R</SUP>Hsp33-bound EF-Tu underwent an unfolding, leading to oligomerization/aggregation. </LI> <LI> EF-Tu oligomers/aggregates became susceptible to degradation by Lon protease. </LI> <LI> Aggregase activity of <SUP>R</SUP>Hsp33 can contribute to proteostasis by dysregulating EF-Tu. </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Empirical Antibiotics in Non-Ventilated Cases of Meconium Aspiration Syndrome
Sung-Min Kang,Chae-Ku Jo,Sun-Young Lee,김묘징 대한신생아학회 2019 Neonatal medicine Vol.26 No.2
Purpose: Meconium aspiration is assumed to be a risk factor for bacterial infection, and patients with meconium aspiration syndrome (MAS) are commonly treated with empiric antibiotics in clinical settings. However, little is known about the effectiveness of the empirical antibiotics treatment. Here, we compared the short-term clinical outcomes associated with empirical antibiotics treatment in non-ventilated cases of MAS. Methods: A retrospective study was conducted on infants admitted with non-ventilated cases of MAS from March 2008 to September 2016. The infants enrolled in the study were divided into two groups based on the antibiotics treatment, and their clinical outcomes were compared. The incidence of sepsis during the hospitalization period and the incidence of delayed sepsis up to 3 months were evaluated. The effects of empirical antibiotic use on respiratory symptoms were evaluated, and the complications were compared. Results: A total of 109 infants were evaluated, of which 61 (56.0%) received antibiotics and 48 (44.0%) did not receive antibiotics. No differences in clinical characteristics were noted between the two groups. However, the empirical antibiotics group showed a significantly higher mean of respiratory rates, C-reactive protein levels, and positive rates, as well as a significantly longer hospitalization period. In clinical outcomes, there were no differences in sepsis rates or respiratory support duration. Furthermore, there were no differences in complications. Conclusion: The empirical use of antibiotics did not affect the clinical outcomes in cases of non-ventilated MAS. The role of empirical antibiotics in these infants may need to be reevaluated.
Ku, Yeonah,Lim, Byung Jin,Yoon, Jo-Hee,Lee, Sang-Jae,An, Kwang-Guk Korean Society of Environmental Biology 2018 환경생물 : 환경생물학회지 Vol.36 No.4
The objective of the study was to determine nutrition regime and limitation in the Boryeng Reservoir where there's a water tunnel between Geum River and the reservoir. Evaluation was conducted through in situ algal bioassay experiments (in situ ABEs) using the cubitainer setting in the reservoirs. For in situ ABEs, we compared and analyzed variations in chlorophyll-a (CHL-a) and phosphorus concentrations in Boryeong Reservoir before and after the water tunnel construction. We then analyzed the nutrient effects on the reservoir. Analysis for nitrogen and phosphorus was done in the three locations of the reservoir and two locations of the ABEs. The in situ ABEs results showed that phosphorous and Nitrogen, the primary limiting nutrient regulating the algal biomass was not limited in the system. The treatments of phosphorus or simultaneous treatments of N+P showed greater algal growth than in the control of nitrate-treatments, indicating a phosphorus deficiency on the phytoplankton growth in the system. The water from the Geum River had 5 times higher total phosphorus (TP) than the water in the reservoir. Efficient management is required as pumping of the river water from Geum River may accelerate the eutrophication of the reservoir.
The reality in the follow-up of breast cancer survivors
Ku Sang Kim,Zisun Kim,Eun-Jung Shim,Nam Hyoung Kim,So-Youn Jung,Jisun Kim,Guiyun Sohn,Jong Won Lee,Jihyoung Cho,Jung Eun Lee,Juhyung Lee,Hyun Jo Youn,Jihyoun Lee,Min Hyuk Lee 대한외과학회 2015 Annals of Surgical Treatment and Research(ASRT) Vol.88 No.3
Purpose: Follow-up after primary treatment for breast cancer is an important component of survivor care and various international guidelines exist for the surveillance. However, little is known about current actual practice patterns of physicians whether they adhere to or deviate from recommended guidelines. The aim of this study was to determine how physicians follow-up their patients after primary treatment for breast cancer in Korea. Methods: A questionnaire survey with 34 questions in 4 categories was e-mailed to the members of Korean Breast Cancer Society from November to December 2013. Respondents were asked how they use follow-up modalities after primary treatment of breast cancer and we compared the survey results with present guidelines. Results: Of the 129 respondents, 123 (95.3%) were breast surgeons. The most important consideration in follow-up was tumor stage. History taking, physical examinations, and mammography were conducted in similar frequency recommended by other guidelines while breast ultrasonography was performed more often. The advanced imaging studies such as CT, MRI, and bone scan, which had been recommended to be conducted only if necessary, were also examined more frequently. Regular screenings for secondary malignancy were performed in 38 respondents (29.5%). Five years later after primary treatment, almost the whole respondents (94.6%) themselves monitored their patients. Conclusion: A majority of respondents have been performed more intensive follow-up modalities in comparison with present guidelines and less frequently screenings for secondary malignancy. For optimal follow-up of breast cancer survivors, tailored delivery system should be considered.
Structural assessment of the tetramerization domain and DNA-binding domain of CP2c
Jo, Ku-Sung,Ryu, Ki-Sung,Yu, Hee-Wan,Lee, Seu-Na,Kim, Ji-Hun,Kim, Eun-Hee,Wang, Chae-Yeon,Kim, Chan-Gil,Kim, Chul Geun,Won, Hyung-Sik Korean Magnetic Resonance Society 2018 Journal of the Korean Magnetic Resonance Society Vol.22 No.4
Although the transcription factor CP2c has been recently validated as a promising target for development of novel anticancer therapy, its structure has not been solved yet. In the present study, the purified recombinant protein corresponding to the tetramerization domain of CP2c appeared to be well folded, whereas the Elf-1 domain showed a largely unfolded conformation. Particularly, the Elf-1 domain, which contains the putative DNA-binding region, showed a conformational equilibrium between relatively less-ordered and well-ordered conformers. Interestingly, addition of zinc shifted the equilibrium to the relatively more structured conformer, whereas zinc binding decreased the overall stability of the protein, leading to a promoted precipitation. Likewise, a dodecapeptide that has been suggested to bind to the Elf-1 domain also appeared to shift the conformational equilibrium and to destabilize the protein. These results constitute the first structural characterization of the CP2c domains and newly suggest that zinc ion might be involved in the conformational regulation of the protein.
Structural assessment of the tetramerization domain and DNA-binding domain of CP2c
Ku-Sung Jo,Ki-Sung Ryu,Hee-Wan Yu,Seu-Na Lee,김지훈,Eun-Hee Kim,Konkuk University,김찬길,김철근,원형식 한국자기공명학회 2018 Journal of the Korean Magnetic Resonance Society Vol.22 No.4
Although the transcription factor CP2c has been recently validated as a promising target for development of novel anticancer therapy, its structure has not been solved yet. In the present study, the purified recombinant protein corresponding to the tetramerization domain of CP2c appeared to be well folded, whereas the Elf-1 domain showed a largely unfolded conformation. Particularly, the Elf-1 domain, which contains the putative DNA-binding region, showed a conformational equilibrium between relatively less-ordered and well-ordered conformers. Interestingly, addition of zinc shifted the equilibrium to the relatively more structured conformer, whereas zinc binding decreased the overall stability of the protein, leading to a promoted precipitation. Likewise, a dodecapeptide that has been suggested to bind to the Elf-1 domain also appeared to shift the conformational equilibrium and to destabilize the protein. These results constitute the first structural characterization of the CP2c domains and newly suggest that zinc ion might be involved in the conformational regulation of the protein.
Backbone NMR Assignments of a Putative p53-binding Domain of the Mitochondrial Hsp40, Tid1
Jo, Ku-Sung,Sim, Dae-Won,Kim, Eun-Hee,Kang, Dong-Hoon,Ma, Yu-Bin,Kim, Ji-Hun,Won, Hyung-Sik Korean Magnetic Resonance Society 2018 Journal of the Korean Magnetic Resonance Society Vol.22 No.3
Human Tid1, belonging to the family of the Hsp40/DnaJ, functions as a co-chaperone of cytosolic and mitochondrial Hsp70 proteins. In addition, the conserved J-domain and G/F-rich region of Tid1 has been suggested to interact with the p53 tumor suppressor protein, to translocate it to the mitochondria. Here, backbone NMR assignments were achieved for the putative p53-binding domain of Tid1. The obtained chemical shift information identified five ${\alpha}$-helices including four helices characteristic of J-domain, which are connected to a short ${\alpha}$-helix in the G/F-rich region via a flexible loop region. We expect that this structural information would contribute to our progressing studies to elucidate atomic structure and molecular interaction of the domain with p53.