title: Ubiquitin-Like Protein SAMP1 and JAMM/MPN+ Metalloprotease HvJAMM1 Constitute a System for Reversible Regulation of Metabolic Enzyme Activity in Archaea.
abstract: Ubiquitin/ubiquitin-like (Ub/Ubl) proteins are involved in diverse cellular processes by their covalent linkage to protein substrates. Here, we provide evidence for a post-translational modification system that regulates enzyme activity which is composed of an archaeal Ubl protein (SAMP1) and a JAMM/MPN+ metalloprotease (HvJAMM1). Molybdopterin (MPT) synthase activity was found to be inhibited by covalent linkage of SAMP1 to the large subunit (MoaE) of MPT synthase. HvJAMM1 was shown to cleave the covalently linked inactive form of SAMP1-MoaE to the free functional individual SAMP1 and MoaE subunits of MPT synthase, suggesting reactivation of MPT synthase by this metalloprotease. Overall, this study provides new insight into the broad idea that Ub/Ubl modification is a post-translational process that can directly and reversibly regulate the activity of metabolic enzymes. In particular, we show that Ub/Ubl linkages on the active site residues of an enzyme (MPT synthase) can inhibit its catalytic activity and that the enzyme can be reactivated through cleavage by a JAMM/MPN+ metalloprotease.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Hepowit
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America; Genetics Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Maupin-Furlow
mesh_terms: D019843:Archaeal Proteins / Q000378:metabolism; D020134:Catalytic Domain; D004789:Enzyme Activation; D019622:Haloferax volcanii / Q000737:chemistry / Q000378:metabolism*; D045726:Metalloproteases / Q000378:metabolism*; D008958:Models, Molecular; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D013466:Sulfurtransferases / Q000378:metabolism*; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019843:Archaeal Proteins; D014452:Ubiquitins; D013466:Sulfurtransferases; C085585:molybdopterin synthase; D045726:Metalloproteases