In a living cell, newly synthesized proteins must flex to gain their functions. This folding can be spontaneous, or with the help of a class of proteins called “companions”. Hsp90 and Hsp70 (also called DnaK in bacteria) are conserved chaperones from bacteria to humans. The model implemented a few years ago shows the cooperation of the two escorts in the laboratory Collapsible form pillars.
To understand the importance of this cooperation He lives In bacteria, the scientists made mutations in Hsp90 in the region of its interaction with DnaK. in home Shewanella oneidensiswhich are aquatic bacteria, they notice them He lives Disruption of the interaction between Hsp90 and DnaK prevents growth during heat stress. This growth defect is associated with a known substrate of Hsp90 called TilS. Thus, they concluded that correct folding of TilS requires cooperation between Hsp90 and DnaK via a direct interaction between the two chaperones. in home Escherichia coli, Mutations that nullify the interaction between Hsp90 and DnaK result in no production of a toxin, colibactin, known to be implicated in the development of cancers in humans. These results demonstrate that cooperation between Hsp90 and DnaK is essential in coli bacteria To produce colibactin, the synthesis of which indirectly requires Hsp90, possibly by folding of one or more proteins of this biosynthesis pathway.
This work reveals for the first time the importance of the cooperation between Hsp90 and DnaK in bacteria, both in stress processes and in the production of toxins by bacteria.
In eukaryotes, cooperation between Hsp90 and DnaK is also known and includes other partners. Thus, the model of cooperation between bacterial Hsp90 and DnaK has evolved towards a more complex system, thus adapting to the challenges of the eukaryotic cell and its proteins.
It is already known that Hsp90 is involved in the pathogenicity of some bacteria. Given the importance of the cooperation between Hsp90 and DnaK in pathogenicitycoli bacteria, This study could open up the development of new molecules to reduce bacterial virulence while multi-resistant bacteria represent a major public health problem.
To find out more:
Uncoupling the activities of Hsp90 and DnaK chaperones revealed the importance of their cooperation in bacteria in vivo.
Corteggiani M, Bossuet-Greif N, Nougayrède JP, Byrne D, Ilbert M, Dementin S, Giudici-Orticoni MT, Méjean V, Oswald E, Genest O.
Proc Natl Acad Sci US A. Sep 13, 2022 doi:10.1073/pnas.2201779119.
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