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Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
Published on: June 21, 2021
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Redox regulation in host-pathogen interactions: thiol switches and beyond.
Marharyta Varatnitskaya1, Adriana Degrossoli2, Lars I Leichert1
1Institute for Biochemistry and Pathobiochemistry - Microbial Biochemistry, Ruhr University Bochum, Bochum, Germany.
Biological Chemistry
|October 6, 2020
Summary
Bacteria and host immune cells use specific strategies to combat hypochlorous acid (HOCl), a potent oxidant. This study explores HOCl
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Organisms constantly interact with pathogens, leading to co-evolution of defense and offense strategies.
- The innate immune system directly encounters bacteria, particularly within phagolysosomes where oxidants are generated.
Purpose of the Study:
- To investigate bacterial and host strategies for counteracting hypochlorous acid (HOCl), a key reactive species.
- To explore the molecular mechanisms of HOCl action on proteins in both pathogens and host immune cells.
- To examine the systemic effects of HOCl on host-pathogen redox homeostasis and signaling.
Main Methods:
- Analysis of bacterial protein modifications induced by HOCl, including thiol-disulfide switches, methionine sulfoxidation, and N-chlorination.
- Investigation of HOCl effects on host proteins and protein homeostasis.
- Utilizing genetically encoded redox probes and redox proteomics to study systemic redox states.
Main Results:
- Gram-negative bacteria employ specific protein modifications (thiol-disulfide switches, methionine oxidation, N-chlorination) to resist HOCl.
- HOCl impacts host protein homeostasis, activating chaperone-like holdases via N-chlorination.
- Systemic analysis reveals distinct redox homeostasis differences between host and pathogen, suggesting novel HOCl signaling pathways.
Conclusions:
- Both bacteria and host immune systems have evolved sophisticated mechanisms to manage HOCl exposure.
- HOCl plays a critical role in host-pathogen interactions, influencing protein function and homeostasis.
- Further research into HOCl signaling pathways may reveal new therapeutic targets for infectious diseases.
Keywords:
N-chlorinationhost-pathogen interactionhypochlorous acidmethionine sulfoxidationneutrophilthiol switchMore Related Videos
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