M. leprae HSP18 suppresses copper (II) mediated ROS generation: Effect of redox stress on its structure and function
Sandip Kumar Nandi1, Ayon Chakraborty1, Alok Kumar Panda1
1School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
Abstract:
Mycobacterium leprae, causative organism of leprosy, is known to counter redox stress generated by reactive oxygen species (ROS) during its survival inside host macrophages. But, the involvement of any antigenic protein(s) for countering such redox stress is still unknown. Interestingly, M. leprae HSP18, an important antigenic protein that helps in the growth and survival of M. leprae pathogen inside host macrophages, is induced under redox stress. Moreover, HSP18 also interacts with Cu2+. Copper (II) can induce redox stress via Fenton reaction. But, whether HSP18 suppresses Cu2+ mediated ROS generation, is still far from clear. Also, the effect of redox stress on its structure and function is not known. In this study, we show that HSP18 efficiently suppresses Cu2+ mediated generation of ROS and also prevents the redox mediated aggregation of a client protein (γD-crystallin). Upon exposure to substantial redox stress, irreversible perturbation in the secondary and tertiary structure of HSP18 and the tryptophan and tyrosine oxidation are evidenced. Interestingly, HSP18 retains a considerable amount of functionality even after being exposed to substantial redox stress. Perhaps, the redox scavenging ability as well as the chaperone function of HSP18 may possibly help M. leprae pathogen to counter redox stress inside host macrophages.
Insights
Mycobacterium leprae HSP18 protein combats copper-induced oxidative stress by suppressing reactive oxygen species (ROS) generation and preventing protein aggregation. This heat shock protein (HSP18) maintains function even under stress, aiding leprosy pathogen survival.
Area of Science:
- Microbiology
- Biochemistry
- Immunology
Background:
- Leprosy is caused by Mycobacterium leprae, which survives host macrophage oxidative stress.
- Antigenic proteins involved in countering this redox stress remain largely unknown.
- Mycobacterium leprae heat shock protein 18 (Hsp18) is induced by redox stress and interacts with copper.
Purpose of the Study:
- To investigate if M. leprae Hsp18 suppresses copper-mediated reactive oxygen species (ROS) generation.
- To determine the effect of redox stress on Hsp18 structure and function.
- To explore Hsp18's role in protecting client proteins from redox damage.
Main Methods:
- Assessing ROS generation in the presence of Hsp18 and copper (II).
- Monitoring client protein (γD-crystallin) aggregation under redox stress with and without Hsp18.
- Analyzing structural changes in Hsp18 using spectroscopic methods after redox stress exposure.
- Evaluating Hsp18's functional activity post-stress.
Main Results:
- Hsp18 significantly suppresses copper-mediated ROS generation.
- Hsp18 prevents the aggregation of the client protein γD-crystallin.
- Redox stress causes irreversible structural changes (secondary, tertiary) and oxidation of tryptophan/tyrosine residues in Hsp18.
- Hsp18 retains substantial functionality despite significant redox stress exposure.
Conclusions:
- M. leprae Hsp18 possesses redox-scavenging and chaperone activities that protect against copper-induced oxidative stress.
- These functions likely contribute to M. leprae survival within host macrophages.
- Hsp18's resilience to redox stress is crucial for the pathogen's persistence.
