A Novel SUMO1-specific Interacting Motif in Dipeptidyl Peptidase 9 (DPP9) That Is Important for Enzymatic Regulation |
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| Authors: | Esther Pilla Ulrike M?ller Guido Sauer Francesca Mattiroli Frauke Melchior Ruth Geiss-Friedlander |
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| Institution: | From the ‡Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Goettingen, Humboldtallee 23, 37073 Goettingen, Germany.;the ¶Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, and ;the ‖Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany |
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| Abstract: | Sumoylation affects many cellular processes by regulating the interactions of modified targets with downstream effectors. Here we identified the cytosolic dipeptidyl peptidase 9 (DPP9) as a SUMO1 interacting protein. Surprisingly, DPP9 binds to SUMO1 independent of the well known SUMO interacting motif, but instead interacts with a loop involving Glu67 of SUMO1. Intriguingly, DPP9 selectively associates with SUMO1 and not SUMO2, due to a more positive charge in the SUMO1-loop. We mapped the SUMO-binding site of DPP9 to an extended arm structure, predicted to directly flank the substrate entry site. Importantly, whereas mutants in the SUMO1-binding arm are less active compared with wild-type DPP9, SUMO1 stimulates DPP9 activity. Consistent with this, silencing of SUMO1 leads to a reduced cytosolic prolyl-peptidase activity. Taken together, these results suggest that SUMO1, or more likely, a sumoylated protein, acts as an allosteric regulator of DPP9. |
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| Keywords: | Peptidases Post-translational Modification Protease SUMO Sumoylation Ubiquitin Dipeptidyl Peptidase SUMO-interacting Motif (SIM) |
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