MsrB1 and MICALs regulate actin assembly and macrophage function via reversible stereoselective methionine oxidation

Mol Cell. 2013 Aug 8;51(3):397-404. doi: 10.1016/j.molcel.2013.06.019. Epub 2013 Aug 1.


Redox control of protein function involves oxidation and reduction of amino acid residues, but the mechanisms and regulators involved are insufficiently understood. Here, we report that in conjunction with Mical proteins, methionine-R-sulfoxide reductase B1 (MsrB1) regulates mammalian actin assembly via stereoselective methionine oxidation and reduction in a reversible, site-specific manner. Two methionine residues in actin are specifically converted to methionine-R-sulfoxide by Mical1 and Mical2 and reduced back to methionine by selenoprotein MsrB1, supporting actin disassembly and assembly, respectively. Macrophages utilize this redox control during cellular activation by stimulating MsrB1 expression and activity as a part of innate immunity. We identified the regulatory role of MsrB1 as a Mical antagonist in orchestrating actin dynamics and macrophage function. More generally, our study shows that proteins can be regulated by reversible site-specific methionine-R-sulfoxidation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism*
  • Animals
  • Cells, Cultured
  • Macrophages / metabolism*
  • Methionine / metabolism*
  • Methionine Sulfoxide Reductases / genetics*
  • Mice
  • Mice, Knockout
  • Microfilament Proteins
  • Microtubule-Associated Proteins / metabolism*
  • Mixed Function Oxygenases / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*


  • Actins
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Methionine
  • Mical1 protein, mouse
  • Mixed Function Oxygenases
  • Oxidoreductases
  • Methionine Sulfoxide Reductases
  • Msrb2 protein, mouse
  • methionine sulfoxide reductase