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PMID: 18799455 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7.

The Journal of biological chemistry ·Vol. 283 ·No. 46 ·2008-11-14 ·Pages 32045-55

Lima CD, Reverter D

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.

MeSH Terms
Amino Acid Sequence Catalytic Domain Crystallography, X-Ray Cysteine Endopeptidases/genetics,metabolism Endopeptidases/genetics,metabolism Humans Models, Molecular Molecular Sequence Data Mutation/genetics Protein Binding SUMO-1 Protein/deficiency,genetics,metabolism Sequence Alignment
Chemicals
SUMO-1 Protein Endopeptidases Cysteine Endopeptidases SENP6 protein, human SENP7 protein, human
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lima Christopher D
Structural Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA. [email protected]
Reverter David
References (46)
46 references, click to expand
  1. The CCP4 suite: programs for protein crystallography.
    Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3 PMID: 15299374
  2. The SUMO-specific protease SENP5 is required for cell division.
    Mol Cell Biol. 2006 Jun;26(12):4489-98 PMID: 16738315
  3. SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae.
    Genes Dev. 2006 Aug 1;20(15):2067-81 PMID: 16847351
  4. Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3.
    Oncogene. 2005 Aug 18;24(35):5401-13 PMID: 15940266
  5. Crystal structure of the SENP1 mutant C603S-SUMO complex reveals the hydrolytic mechanism of SUMO-specific protease.
    Biochem J. 2006 Sep 15;398(3):345-52 PMID: 16712526
  6. A basis for SUMO protease specificity provided by analysis of human Senp2 and a Senp2-SUMO complex.
    Structure. 2004 Aug;12(8):1519-31 PMID: 15296745
  7. DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1.
    J Biol Chem. 2003 Aug 1;278(31):28882-91 PMID: 12759363
  8. The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast.
    J Biol Chem. 2003 Nov 7;278(45):44113-20 PMID: 12941945
  9. Coot: model-building tools for molecular graphics.
    Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32 PMID: 15572765
  10. Identification and characterization of DEN1, a deneddylase of the ULP family.
    J Biol Chem. 2003 Aug 1;278(31):28892-900 PMID: 12759362
  11. Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway.
    Nat Cell Biol. 2008 May;10(5):547-55 PMID: 18408733
  12. Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex.
    Mol Cell Biol. 2002 Sep;22(18):6498-508 PMID: 12192048
  13. The ubiquitin system.
    Annu Rev Biochem. 1998;67:425-79 PMID: 9759494
  14. Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3.
    J Biol Chem. 2006 Jun 9;281(23):15869-77 PMID: 16608850
  15. Concepts in sumoylation: a decade on.
    Nat Rev Mol Cell Biol. 2007 Dec;8(12):947-56 PMID: 18000527
  16. Protein modification by SUMO.
    Annu Rev Biochem. 2004;73:355-82 PMID: 15189146
  17. SUMO protease SENP1 induces isomerization of the scissile peptide bond.
    Nat Struct Mol Biol. 2006 Dec;13(12):1069-77 PMID: 17099698
  18. A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus.
    J Biol Chem. 2004 Jun 25;279(26):27233-8 PMID: 15123604
  19. SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia.
    Cell. 2007 Nov 2;131(3):584-95 PMID: 17981124
  20. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids.
    Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83 PMID: 17452350
  21. Crystallography & NMR system: A new software suite for macromolecular structure determination.
    Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 PMID: 9757107
  22. Processing of X-ray diffraction data collected in oscillation mode.
    Methods Enzymol. 1997;276:307-26 PMID: 27754618
  23. Modification of proteins by ubiquitin and ubiquitin-like proteins.
    Annu Rev Cell Dev Biol. 2006;22:159-80 PMID: 16753028
  24. Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3.
    J Biol Chem. 2000 Mar 3;275(9):6252-8 PMID: 10692421
  25. Characterization of the localization and proteolytic activity of the SUMO-specific protease, SENP1.
    J Biol Chem. 2004 Jan 2;279(1):692-703 PMID: 14563852
  26. Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1.
    J Mol Biol. 2005 Jan 7;345(1):141-51 PMID: 15567417
  27. Positive and negative regulation of APP amyloidogenesis by sumoylation.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):259-64 PMID: 12506199
  28. Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast.
    Mol Cell. 2000 May;5(5):865-76 PMID: 10882122
  29. Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.
    Nat Struct Mol Biol. 2006 Dec;13(12):1060-8 PMID: 17099700
  30. Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1.
    EMBO J. 2005 Apr 6;24(7):1341-51 PMID: 15775960
  31. SUSP1 antagonizes formation of highly SUMO2/3-conjugated species.
    J Cell Biol. 2006 Sep 25;174(7):939-49 PMID: 17000875
  32. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  33. Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics.
    Mol Cell Proteomics. 2006 Dec;5(12):2298-310 PMID: 17000644
  34. A novel mammalian Smt3-specific isopeptidase 1 (SMT3IP1) localized in the nucleolus at interphase.
    Eur J Biochem. 2000 Nov;267(21):6423-7 PMID: 11029585
  35. Distinct in vivo dynamics of vertebrate SUMO paralogues.
    Mol Biol Cell. 2004 Dec;15(12):5208-18 PMID: 15456902
  36. Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes.
    Mol Cell. 2006 Feb 3;21(3):349-57 PMID: 16455490
  37. Mutation of SENP1/SuPr-2 reveals an essential role for desumoylation in mouse development.
    Mol Cell Biol. 2005 Jun;25(12):5171-82 PMID: 15923632
  38. A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation.
    Biochem Biophys Res Commun. 2005 Nov 18;337(2):517-20 PMID: 16198310
  39. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9.
    J Biol Chem. 2001 Sep 21;276(38):35368-74 PMID: 11451954
  40. Association of the human SUMO-1 protease SENP2 with the nuclear pore.
    J Biol Chem. 2002 May 31;277(22):19961-6 PMID: 11896061
  41. A new protease required for cell-cycle progression in yeast.
    Nature. 1999 Mar 18;398(6724):246-51 PMID: 10094048
  42. Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family.
    Biochem J. 2008 Jan 15;409(2):461-9 PMID: 17916063
  43. Automated MAD and MIR structure solution.
    Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61 PMID: 10089316
  44. Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs.
    J Biol Chem. 2007 Sep 7;282(36):26217-24 PMID: 17591783
  45. Modification in reverse: the SUMO proteases.
    Trends Biochem Sci. 2007 Jun;32(6):286-95 PMID: 17499995
  46. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation.
    Nat Cell Biol. 2008 May;10(5):538-46 PMID: 18408734
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M805655200
Email
[email protected]
Published
2008-11-14
Epub
2008-00-16
Pages
32045-55
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2581585
Subset
IM
Grants
NIGMS NIH HHS · GM65872 · United States
NCRR NIH HHS · P41 RR015301 · United States
NIGMS NIH HHS · R01 GM065872-07 · United States
NCRR NIH HHS · RR-15301 · United States
NIGMS NIH HHS · R01 GM065872-08 · United States
NIGMS NIH HHS · R01 GM065872-09 · United States
NIGMS NIH HHS · R01 GM065872 · United States
External Links
PubMed source DOI: 10.1074/jbc.M805655200 PMC Full Text View journal details
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