title: A novel SUMO1-specific interacting motif in dipeptidyl peptidase 9 (DPP9) that is important for enzymatic regulation.
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 Glu(67) 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.
authors.affiliation: Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Goettingen, Humboldtallee 23, 37073 Goettingen, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Pilla
authors.forename: Ulrike
authors.initials: U
authors.lastname: Möller
authors.forename: Guido
authors.initials: G
authors.lastname: Sauer
authors.forename: Francesca
authors.initials: F
authors.lastname: Mattiroli
authors.forename: Frauke
authors.initials: F
authors.lastname: Melchior
authors.forename: Ruth
authors.initials: R
authors.lastname: Geiss-Friedlander
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation
chemical_list: D025842:SUMO-1 Protein; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases