Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7.
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.
Lima
Christopher D
CD
Structural Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA. limac@mskcc.org
Reverter
David
D
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
D025842:SUMO-1 Protein; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C408873:SENP6 protein, human; C533959:SENP7 protein, human
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