title: Swapping small ubiquitin-like modifier (SUMO) isoform specificity of SUMO proteases SENP6 and SENP7.
abstract: SUMO proteases can regulate the amounts of SUMO-conjugated proteins in the cell by cleaving off the isopeptidic bond between SUMO and the target protein. Of the six members that constitute the human SENP/ULP protease family, SENP6 and SENP7 are the most divergent members in their conserved catalytic domain. The SENP6 and SENP7 subclass displays a clear proteolytic cleavage preference for SUMO2/3 isoforms. To investigate the structural determinants for such isoform specificity, we have identified a unique sequence insertion in the SENP6 and SENP7 subclass that is essential for their proteolytic activity and that forms a more extensive interface with SUMO during the proteolytic reaction. Furthermore, we have identified a region in the SUMO surface determinant for the SUMO2/3 isoform specificity of SENP6 and SENP7. Double point amino acid mutagenesis on the SUMO surface allows us to swap the specificity of SENP6 and SENP7 between the two SUMO isoforms. Structure-based comparisons combined with biochemical and mutagenesis analysis have revealed Loop 1 insertion in SENP6 and SENP7 as a platform to discriminate between SUMO1 and SUMO2/3 isoforms in this subclass of the SUMO protease family.
authors: Departament de Bioquimica i Biologia Molecular, Institut de Biotecnologia i de Biomedicina, Universitat Autonoma de Barcelona, 08193 Barcelona, Spain.
authors: Kamela O
authors: KO
authors: Alegre
authors: Departament de Bioquimica i Biologia Molecular, Institut de Biotecnologia i de Biomedicina, Universitat Autonoma de Barcelona, 08193 Barcelona, Spain. Electronic address: david.reverter@uab.cat.
authors: David
authors: D
authors: Reverter
mesh_terms: D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D059748:Proteolysis; D025842:SUMO-1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000502:physiology; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C408873:SENP6 protein, human; C533959:SENP7 protein, human