title: MsrB1 and MICALs regulate actin assembly and macrophage function via reversible stereoselective methionine oxidation.
abstract: 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.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Byung Cheon
authors.initials: BC
authors.lastname: Lee
authors.forename: Zalán
authors.initials: Z
authors.lastname: Péterfi
authors.forename: Fukun W
authors.initials: FW
authors.lastname: Hoffmann
authors.forename: Richard E
authors.initials: RE
authors.lastname: Moore
authors.forename: Alaattin
authors.initials: A
authors.lastname: Kaya
authors.forename: Andrei
authors.initials: A
authors.lastname: Avanesov
authors.forename: Lionel
authors.initials: L
authors.lastname: Tarrago
authors.forename: Yani
authors.initials: Y
authors.lastname: Zhou
authors.forename: Eranthie
authors.initials: E
authors.lastname: Weerapana
authors.forename: Dmitri E
authors.initials: DE
authors.lastname: Fomenko
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hoffmann
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D008264:Macrophages / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism*; D051150:Methionine Sulfoxide Reductases / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D008715:Methionine; C507541:Mical1 protein, mouse; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C520510:Msrb2 protein, mouse; C027219:methionine sulfoxide reductase
references.citation: J Biol Chem. 2009 Feb 13;284(7):4354-64
references.pmid: 19049972
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12920-5
references.pmid: 11606777
references.citation: J Cell Biol. 2012 Jul 23;198(2):155-64
references.pmid: 22826120
references.citation: J Biol Chem. 2012 Feb 10;287(7):4492-502
references.pmid: 22205701
references.citation: Biochemistry. 2006 Dec 12;45(49):14642-54
references.pmid: 17144657
references.citation: Antioxid Redox Signal. 2003 Oct;5(5):577-82
references.pmid: 14580313
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9932-7
references.pmid: 9275229
references.citation: Annu Rev Immunol. 1999;17:593-623
references.pmid: 10358769
references.citation: J Immunol. 1987 Jan 1;138(1):32-6
references.pmid: 3491159
references.citation: Annu Rev Biochem. 2012;81:661-86
references.pmid: 22663081
references.citation: Cell. 2008 May 2;133(3):462-74
references.pmid: 18455987
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4245-50
references.pmid: 11929995
references.citation: J Cell Biochem. 2012 Jan;113(1):80-92
references.pmid: 21898535
references.citation: J Biol Chem. 2009 Feb 27;284(9):5986-93
references.pmid: 18990697
references.citation: J Physiol. 2006 Mar 1;571(Pt 2):329-48
references.pmid: 16396928
references.citation: Nature. 2010 Feb 11;463(7282):823-7
references.pmid: 20148037
references.citation: Biochemistry. 2005 Jun 7;44(22):8059-67
references.pmid: 15924425
references.citation: Nat Rev Mol Cell Biol. 2004 Aug;5(8):647-57
references.pmid: 15366708
references.citation: Antioxid Redox Signal. 2010 Apr 1;12(7):829-38
references.pmid: 19769460
references.citation: J Cell Sci. 2012 Feb 1;125(Pt 3):614-24
references.pmid: 22331357
references.citation: Cytoskeleton (Hoboken). 2010 Oct;67(10):609-29
references.pmid: 20672362
references.citation: Antioxid Redox Signal. 2010 Aug 15;13(4):539-49
references.pmid: 19958171
references.citation: Arch Biochem Biophys. 2002 Jan 15;397(2):172-8
references.pmid: 11795868
references.citation: Mol Cell Biochem. 2002 May-Jun;234-235(1-2):3-9
references.pmid: 12162447
references.citation: J Gerontol. 1992 Mar;47(2):B37-44
references.pmid: 1538058
references.citation: Science. 2011 Dec 23;334(6063):1710-3
references.pmid: 22116028
references.citation: Nat Rev Mol Cell Biol. 2011 Dec 22;13(1):39-51
references.pmid: 22189424
references.citation: Biochim Biophys Acta. 2009 Nov;1790(11):1471-7
references.pmid: 19406207
references.citation: Free Radic Biol Med. 2013 Aug;61:257-64
references.pmid: 23583331
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9493-8
references.pmid: 23690622
references.citation: J Proteome Res. 2010 Mar 5;9(3):1598-609
references.pmid: 20063901
references.citation: PLoS Biol. 2005 Dec;3(12):e375
references.pmid: 16262444
references.citation: Antioxid Redox Signal. 2007 Jan;9(1):1-24
references.pmid: 17115885
references.citation: Lancet. 2012 Mar 31;379(9822):1256-68
references.pmid: 22381456
references.citation: Nature. 2009 Mar 26;458(7237):430-7
references.pmid: 19325622