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- Title
ClpL Chaperone as a Possible Component of the Disaggregase Activity of Limosilactobacillus fermentum U-21.
- Authors
Al Ebrahim, Rahaf N.; Alekseeva, Maria G.; Bazhenov, Sergey V.; Fomin, Vadim V.; Mavletova, Dilara A.; Nesterov, Andrey A.; Poluektova, Elena U.; Danilenko, Valeriy N.; Manukhov, Ilya V.
- Abstract
Simple Summary: The increase in the average life expectancy of people, the deterioration of the environment, and the stress of various etiologies, all these reasons contribute to the rising prevalence of Parkinson's disease. With this, the relevance of developing drugs for the prevention and treatment of it increases. Parkinson's disease is accompanied by a disruption of the protein structure and inflammatory processes. One of the approaches to combating this disease is the use of pharmabiotics based on bacteria that are able to produce enzymes that help maintain the native structure of proteins, i.e., possessing chaperone activity. Previously, L. fermentum U-21 has demonstrated the potential for use as a pharmabiotic. This study focuses on one of the proteins secreted by these bacteria, whose activity can help maintain the native state of proteins in patient tissues. We demonstrated the chaperone activity of the mixture of proteins secreted by L. fermentum U-21 cells and the presence of ClpL among these proteins. In vivo and in vitro tests showed the chaperone activity of ClpL. These findings indicate an involvement of the ClpL chaperone in the disaggregase activity and pharmabiotic properties of L. fermentum U-21. The L. fermentum U-21 strain, known for secreting chaperones into the extracellular milieu, emerges as a promising candidate for the development of novel therapeutics termed disaggregases for Parkinson's disease. Our study focuses on characterizing the secreted protein encoded by the C0965_000195 locus in the genome of this strain. Through sequence analysis and structural predictions, the protein encoded by C0965_000195 is identified as ClpL, homologs of which are known for their chaperone functions. The chaperone activity of ClpL from L. fermentum U-21 is investigated in vivo by assessing the refolding of luciferases with varying thermostabilities from Aliivibrio fischeri and Photorhabdus luminescens within Escherichia coli cells. The results indicate that the clpL gene from L. fermentum U-21 can compensate for the absence of the clpB gene, enhancing the refolding capacity of thermodenatured proteins in clpB-deficient cells. In vitro experiments demonstrate that both spent culture medium containing proteins secreted by L. fermentum U-21 cells, including ClpL, and purified heterologically expressed ClpL partially prevent the thermodenaturation of luciferases. The findings suggest that the ClpL protein from L. fermentum U-21, exhibiting disaggregase properties against aggregating proteins, may represent a key component contributing to the pharmabiotic attributes of this strain.
- Subjects
PARKINSON'S disease; PHOTORHABDUS luminescens; BACTERIAL proteins; PROTEIN structure; LUCIFERASES
- Publication
Biology (2079-7737), 2024, Vol 13, Issue 8, p592
- ISSN
2079-7737
- Publication type
Article
- DOI
10.3390/biology13080592