title: Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7.
abstract: Small ubiquitin-like modifier (SUMO) proteases regulate the abundance and lifetime of SUMO-conjugated substrates by antagonizing reactions catalyzed by SUMO-conjugating enzymes. Six SUMO proteases constitute the human SENP/ULP protease family (SENP1-3 and SENP5-7). SENP6 and SENP7 include the most divergent class of SUMO proteases, which also includes the yeast enzyme ULP2. We present the crystal structure of the SENP7 catalytic domain at a resolution of 2.4 angstroms. Comparison with structures of human SENP1 and SENP2 reveals unique elements that differ from previously characterized structures of SUMO-deconjugating enzymes. Biochemical assays show that SENP6 and SENP7 prefer SUMO2 or SUMO3 in deconjugation reactions with rates comparable with those catalyzed by SENP2, particularly during cleavage of di-SUMO2, di-SUMO3, and poly-SUMO chains composed of SUMO2 or SUMO3. In contrast, SENP6 and SENP7 exhibit lower rates for processing pre-SUMO1, pre-SUMO2, or pre-SUMO3 in comparison with SENP2. Structure-guided mutational analysis reveals elements unique to the SENP6 and SENP7 subclass of SENP/ULP proteases that contribute to protease function during deconjugation of poly-SUMO chains.
authors.affiliation: Structural Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA. limac@mskcc.org
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lima
authors.forename: David
authors.initials: D
authors.lastname: Reverter
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D025842:SUMO-1 Protein; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C408873:SENP6 protein, human; C533959:SENP7 protein, human
references.citation: Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
references.pmid: 15299374
references.citation: Mol Cell Biol. 2006 Jun;26(12):4489-98
references.pmid: 16738315
references.citation: Genes Dev. 2006 Aug 1;20(15):2067-81
references.pmid: 16847351
references.citation: Oncogene. 2005 Aug 18;24(35):5401-13
references.pmid: 15940266
references.citation: Biochem J. 2006 Sep 15;398(3):345-52
references.pmid: 16712526
references.citation: Structure. 2004 Aug;12(8):1519-31
references.pmid: 15296745
references.citation: J Biol Chem. 2003 Aug 1;278(31):28882-91
references.pmid: 12759363
references.citation: J Biol Chem. 2003 Nov 7;278(45):44113-20
references.pmid: 12941945
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: J Biol Chem. 2003 Aug 1;278(31):28892-900
references.pmid: 12759362
references.citation: Nat Cell Biol. 2008 May;10(5):547-55
references.pmid: 18408733
references.citation: Mol Cell Biol. 2002 Sep;22(18):6498-508
references.pmid: 12192048
references.citation: Annu Rev Biochem. 1998;67:425-79
references.pmid: 9759494
references.citation: J Biol Chem. 2006 Jun 9;281(23):15869-77
references.pmid: 16608850
references.citation: Nat Rev Mol Cell Biol. 2007 Dec;8(12):947-56
references.pmid: 18000527
references.citation: Annu Rev Biochem. 2004;73:355-82
references.pmid: 15189146
references.citation: Nat Struct Mol Biol. 2006 Dec;13(12):1069-77
references.pmid: 17099698
references.citation: J Biol Chem. 2004 Jun 25;279(26):27233-8
references.pmid: 15123604
references.citation: Cell. 2007 Nov 2;131(3):584-95
references.pmid: 17981124
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83
references.pmid: 17452350
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
references.pmid: 9757107
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: Annu Rev Cell Dev Biol. 2006;22:159-80
references.pmid: 16753028
references.citation: J Biol Chem. 2000 Mar 3;275(9):6252-8
references.pmid: 10692421
references.citation: J Biol Chem. 2004 Jan 2;279(1):692-703
references.pmid: 14563852
references.citation: J Mol Biol. 2005 Jan 7;345(1):141-51
references.pmid: 15567417
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):259-64
references.pmid: 12506199
references.citation: Mol Cell. 2000 May;5(5):865-76
references.pmid: 10882122
references.citation: Nat Struct Mol Biol. 2006 Dec;13(12):1060-8
references.pmid: 17099700
references.citation: EMBO J. 2005 Apr 6;24(7):1341-51
references.pmid: 15775960
references.citation: J Cell Biol. 2006 Sep 25;174(7):939-49
references.pmid: 17000875
references.citation: Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9
references.pmid: 2025413
references.citation: Mol Cell Proteomics. 2006 Dec;5(12):2298-310
references.pmid: 17000644
references.citation: Eur J Biochem. 2000 Nov;267(21):6423-7
references.pmid: 11029585
references.citation: Mol Biol Cell. 2004 Dec;15(12):5208-18
references.pmid: 15456902
references.citation: Mol Cell. 2006 Feb 3;21(3):349-57
references.pmid: 16455490
references.citation: Mol Cell Biol. 2005 Jun;25(12):5171-82
references.pmid: 15923632
references.citation: Biochem Biophys Res Commun. 2005 Nov 18;337(2):517-20
references.pmid: 16198310
references.citation: J Biol Chem. 2001 Sep 21;276(38):35368-74
references.pmid: 11451954
references.citation: J Biol Chem. 2002 May 31;277(22):19961-6
references.pmid: 11896061
references.citation: Nature. 1999 Mar 18;398(6724):246-51
references.pmid: 10094048
references.citation: Biochem J. 2008 Jan 15;409(2):461-9
references.pmid: 17916063
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61
references.pmid: 10089316
references.citation: J Biol Chem. 2007 Sep 7;282(36):26217-24
references.pmid: 17591783
references.citation: Trends Biochem Sci. 2007 Jun;32(6):286-95
references.pmid: 17499995
references.citation: Nat Cell Biol. 2008 May;10(5):538-46
references.pmid: 18408734