title: Structural and functional analysis of Nro1/Ett1: a protein involved in translation termination in S. cerevisiae and in O2-mediated gene control in S. pombe.
abstract: In Saccharomyces cerevisiae, the putative 2-OG-Fe(II) dioxygenase Tpa1 and its partner Ett1 have been shown to impact mRNA decay and translation. Hence, inactivation of these factors was shown to influence stop codon read-though. In addition, Tpa1 represses, by an unknown mechanism, genes regulated by Hap1, a transcription factor involved in the response to levels of heme and O(2). The Schizosaccharomyces pombe orthologs of Tpa1 and Ett1, Ofd1, and its partner Nro1, respectively, have been shown to regulate the stability of the Sre1 transcription factor in response to oxygen levels. To gain insight into the function of Nro1/Ett1, we have solved the crystal structure of the S. pombe Nro1 protein deleted of its 54 N-terminal residues. Nro1 unexpectedly adopts a Tetratrico Peptide Repeat (TPR) fold, a motif often responsible for protein or peptide binding. Two ligands, a sulfate ion and an unknown molecule, interact with a cluster of highly conserved amino acids on the protein surface. Mutation of these residues demonstrates that these ligand binding sites are essential for Ett1 function in S. cerevisiae, as investigated by assaying for efficient translation termination.
authors: CNRS UMR7104, Inserm U964, Université de Strasbourg, Strasbourg, Illkirch F-67000, France.
authors: Delphine
authors: D
authors: Rispal
authors: Julien
authors: J
authors: Henri
authors: Herman
authors: H
authors: van Tilbeurgh
authors: Marc
authors: M
authors: Graille
authors: Bertrand
authors: B
authors: Séraphin
references: J Biol Chem. 2003 Sep 12;278(37):34966-74
references: 12824157
references: J Biol Chem. 2007 Aug 17;282(33):24388-96
references: 17595166
references: Acta Crystallogr D Biol Crystallogr. 2003 Nov;59(Pt 11):2023-30
references: 14573958
references: Acta Crystallogr D Biol Crystallogr. 2002 Oct;58(Pt 10 Pt 2):1772-9
references: 12351820
references: Bioinformatics. 2008 Dec 1;24(23):2780-1
references: 18818215
references: Nature. 2006 Mar 30;440(7084):637-43
references: 16554755
references: J Bacteriol. 1983 Jan;153(1):163-8
references: 6336730
references: RNA. 1999 Aug;5(8):1014-20
references: 10445876
references: Biochem Biophys Res Commun. 2006 Feb 24;340(4):1028-38
references: 16403447
references: Genes Dev. 2008 May 1;22(9):1115-40
references: 18451103
references: Nucleic Acids Res. 2009 Jan;37(1):129-43
references: 19033360
references: J Biol Chem. 2010 May 28;285(22):16683-92
references: 20371601
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15764-9
references: 14671320
references: Mol Cell. 2009 May 14;34(4):440-50
references: 19481524
references: Mol Cell Biol. 2006 Apr;26(7):2817-31
references: 16537923
references: Cell. 2008 Aug 22;134(4):624-33
references: 18724935
references: Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17575-9
references: 20876129
references: Genes Dev. 2009 May 1;23(9):1106-18
references: 19417105
references: Cell. 2006 Jun 16;125(6):1125-36
references: 16777602
references: J Biol Chem. 2006 Oct 6;281(40):30175-85
references: 16857670
references: EMBO Rep. 2010 Mar;11(3):214-9
references: 20062004
references: Proteins. 2004 Mar 1;54(4):776-83
references: 14997573
references: Structure. 2011 Apr 13;19(4):503-14
references: 21481773
references: EMBO J. 2008 May 21;27(10):1491-501
references: 18418381
references: Nature. 2006 Mar 23;440(7083):561-4
references: 16554824
references: EMBO J. 1995 Aug 15;14(16):4065-72
references: 7664746
references: J Biol Chem. 2008 Mar 14;283(11):7145-54
references: 18180287
references: Mol Cell. 1999 Jul;4(1):21-33
references: 10445024
references: J Biol Chem. 2010 Oct 1;285(40):30767-78
references: 20630870
references: J Mol Biol. 2009 Dec 4;394(3):410-22
references: 19733178
references: Bioinformatics. 1999 Apr;15(4):305-8
references: 10320398
references: Nucleic Acids Res. 2003 Jul 1;31(13):3497-500
references: 12824352
references: Nat Struct Mol Biol. 2010 Dec;17(12):1446-52
references: 21102444
references: EMBO J. 2001 Nov 1;20(21):5822-31
references: 11689423
references: Gene. 1992 Jan 2;110(1):119-22
references: 1544568
references: Biochem Biophys Res Commun. 2004 Apr 30;317(2):342-51
references: 15063763
references: EMBO J. 2003 Mar 3;22(5):1158-67
references: 12606580
references: Science. 2010 Oct 15;330(6002):369-72
references: 20947765
references: Nat Struct Mol Biol. 2010 Oct;17(10):1233-40
references: 20890290
references: J Cell Biol. 2000 Feb 21;148(4):635-51
references: 10684247
references: Genetics. 2009 Jan;181(1):93-103
references: 19015546
references: J Biol Chem. 2009 Jun 26;284(26):17641-7
references: 19419969
references: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references: 15572765
references: J Biol Chem. 2004 Jun 4;279(23):24323-33
references: 15044472
references: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references: 12393927
references: Cell. 2007 Nov 16;131(4):660-8
references: 18022361
references: Science. 2007 Feb 2;315(5812):646-9
references: 17272721
references: Cell. 2005 Mar 25;120(6):831-42
references: 15797383
references: Cell. 2000 Feb 4;100(3):311-21
references: 10676813
references: Mol Cell Biol. 2002 Apr;22(8):2564-74
references: 11909951
references: EMBO J. 2009 Jan 21;28(2):135-43
references: 19158663
references: Science. 1995 Dec 1;270(5241):1464-72
references: 7491491
references: Mol Cell Biol. 2006 Jul;26(14):5237-48
references: 16809762
references: J Biol Chem. 2005 Apr 15;280(15):14645-55
references: 15705570
references: Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8348-53
references: 15159550
references: EMBO J. 1990 May;9(5):1665-72
references: 2184035
references: Nucleic Acids Res. 2010 Apr;38(6):2099-110
references: 20040577
references: J Mol Biol. 1995 Aug 18;251(3):334-45
references: 7650736
references: Gene. 1994 Dec 15;150(2):395-9
references: 7821814
references: Trends Biochem Sci. 2003 Dec;28(12):655-62
references: 14659697
references: RNA. 2002 Feb;8(2):129-36
references: 11911360
references: Mol Cell Biol. 2002 May;22(10):3301-15
references: 11971964
references: Yeast. 2004 Apr 30;21(6):495-509
references: 15116432
references: Mol Cell. 2004 Apr 23;14(2):233-45
references: 15099522
references: Yeast. 2000 Jun 30;16(9):857-60
references: 10861908
references: J Biol Chem. 2004 Dec 10;279(50):52255-61
references: 15456751
references: Mol Cell. 1999 Jul;4(1):85-95
references: 10445030