Available online 7 September 2022

Met residues can be oxidized to Met sulfoxide and reduced by methionine sulfoxide reductases (MSR).

The selenoprotein MSRB1 is present in animals and its expression regulated by dietary selenium.

MSRB1 protects against oxidative stress but few targets are known.

MSRB1 regulates actin polymerization in a cycle of Met oxidation/reduction with MICALs enzymes.

CaMKII and CaM oxidation and reduction by MSRB1 may protect cardiac and nervous cells.

Methionine (Met) can be oxidized to methionine sulfoxide (MetO), which exist as R- and S-diastereomers. Present in all three domains of life, methionine sulfoxide reductases (MSR) are the enzymes that reduce MetO back to Met. Most characterized among them are MSRA and MSRB, which are strictly stereospecific for the S- and R-diastereomers of MetO, respectively. While the majority of MSRs use a catalytic Cys to reduce their substrates, some employ selenocysteine. This is the case of mammalian MSRB1, which was initially discovered as selenoprotein SELR or SELX and later was found to exhibit an MSRB activity. Genomic analyses demonstrated its occurrence in most animal lineages, and biochemical and structural analyses uncovered its catalytic mechanism. The use of transgenic mice and mammalian cell culture revealed its physiological importance in the protection against oxidative stress, maintenance of neuronal cells, cognition, cancer cell proliferation, and the immune response. Coincident with the discovery of Met oxidizing MICAL enzymes, recent findings of MSRB1 regulating the innate immunity response through reversible stereospecific Met-R-oxidation of cytoskeletal actin opened up new avenues for biological importance of MSRB1 and its role in disease. In this review, we discuss the current state of research on MSRB1, compare it with other animal Msrs, and offer a perspective on further understanding of biological functions of this selenoprotein.

Methionine sulfoxide

Methionine sulfoxide reductase

Oxidative stress

Protein oxidation

Redox signaling

Selenoprotein

Selenium

this is a review

© 2022 Published by Elsevier Inc.