title: Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast.
abstract: Modification of cellular proteins by the ubiquitin-like protein SUMO is essential for nuclear processes and cell cycle progression in yeast. The Ulp1 protease catalyzes two essential functions in the SUMO pathway: (1) processing of full-length SUMO to its mature form and (2) deconjugation of SUMO from targeted proteins. Selective reduction of the proteolytic reaction produced a covalent thiohemiacetal transition state complex between a Ulp1 C-terminal fragment and its cellular substrate Smt3, the yeast SUMO homolog. The Ulp1-Smt3 crystal structure and functional testing of elements within the conserved interface elucidate determinants of SUMO recognition, processing, and deconjugation. Genetic analysis guided by the structure further reveals a regulatory element N-terminal to the proteolytic domain that is required for cell growth in yeast.
authors.affiliation: Biochemistry Department, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: E
authors.initials: E
authors.lastname: Mossessova
authors.forename: C D
authors.initials: CD
authors.lastname: Lima
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry*; D005998:Glycine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D025841:Small Ubiquitin-Related Modifier Proteins; D013379:Substrate Specificity; D013499:Surface Properties; D014452:Ubiquitins / Q000737:chemistry*
chemical_list: D005656:Fungal Proteins; D010446:Peptide Fragments; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; C118083:Ulp1 protease; D005998:Glycine