| Autor: |
Al Ebrahim RN; Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia., Alekseeva MG; Laboratory of Genetics of Microorganisms, Vavilov Institute of General Genetics Russian Academy of Sciences, 119991 Moscow, Russia., Bazhenov SV; Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia., Fomin VV; Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia.; Laboratory of Microbiology, BIOTECH University, 125080 Moscow, Russia., Mavletova DA; Laboratory of Genetics of Microorganisms, Vavilov Institute of General Genetics Russian Academy of Sciences, 119991 Moscow, Russia., Nesterov AA; Laboratory of Genetics of Microorganisms, Vavilov Institute of General Genetics Russian Academy of Sciences, 119991 Moscow, Russia.; Institute of Environmental Engineering, RUDN University, 117198 Moscow, Russia., Poluektova EU; Laboratory of Genetics of Microorganisms, Vavilov Institute of General Genetics Russian Academy of Sciences, 119991 Moscow, Russia., Danilenko VN; Laboratory of Genetics of Microorganisms, Vavilov Institute of General Genetics Russian Academy of Sciences, 119991 Moscow, Russia.; Research Center of Neurology, 125367 Moscow, Russia., Manukhov IV; Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia. |
| Abstrakt: |
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. |
