Functional characterization of the Aspergillus nidulans methionine sulfoxide reductases (msrA and msrB)

Frederico Marianetti Soriani1, Marcia Regina Kress, Paula Fagundes de Gouvêa

  • 1Departamento de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, Brazil.

Insights

Methionine sulfoxide reductases (MsrA and MsrB) protect proteins from oxidative damage in Aspergillus nidulans. Inactivation mutants showed increased sensitivity to oxidative stress, highlighting the enzymes' crucial protective role.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Mycology

Background:

  • Proteins are susceptible to oxidative damage from reactive oxygen species (ROS).
  • Oxidation of methionine residues forms methionine sulfoxide [Met(O)], impairing protein function and cellular homeostasis.
  • Methionine sulfoxide reductases (MsrA and MsrB) repair these oxidative modifications.

Purpose of the Study:

  • To identify and characterize the homologs of methionine sulfoxide reductases (msrA and msrB) in the filamentous fungus Aspergillus nidulans.
  • To investigate the role of MsrA and MsrB in protecting fungal proteins against oxidative stress.

Main Methods:

  • Gene identification and characterization of msrA and msrB in Aspergillus nidulans.
  • Construction and analysis of single and double msrA/msrB inactivation mutants.
  • Assessment of mutant sensitivity to oxidative stress agents (hydrogen peroxide, paraquat, UV light).
  • Quantification of carbonylated proteins in wild-type and mutant strains under oxidative stress.

Main Results:

  • Both msrA and msrB homologs were identified in Aspergillus nidulans.
  • Single and double msrA/msrB mutants were viable but exhibited increased sensitivity to hydrogen peroxide, paraquat, and UV light.
  • Mutant strains accumulated significantly higher levels of carbonylated proteins upon exposure to hydrogen peroxide compared to wild-type.

Conclusions:

  • MsrA and MsrB play a critical role in protecting cellular proteins from oxidative damage in Aspergillus nidulans.
  • These enzymes are essential for maintaining cellular homeostasis under oxidative stress conditions.
  • The findings underscore the conserved importance of methionine sulfoxide reductases in combating oxidative damage across different organisms.

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