title: A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes.
abstract: Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2∼Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s.
authors.affiliation: Department of Biology, Saint Louis University, 3507 Laclede Avenue, St Louis, MO 63103, USA.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 S, Grand Avenue, St Louis, MO 63104, USA.
authors.forename: Konstantin R
authors.initials: KR
authors.lastname: Malley
authors.affiliation: Department of Biology, Saint Louis University, 3507 Laclede Avenue, St Louis, MO 63103, USA.
authors.forename: Caitlin C
authors.initials: CC
authors.lastname: Brenner
authors.affiliation: Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 S, Grand Avenue, St Louis, MO 63104, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Koroleva
authors.affiliation: Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 S, Grand Avenue, St Louis, MO 63104, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Korolev
authors.affiliation: Department of Biology, Saint Louis University, 3507 Laclede Avenue, St Louis, MO 63103, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Downes
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D018360:Crystallography, X-Ray; D056890:Eukaryota / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D000072417:Protein Domains; D017368:Protein Prenylation; D017386:Sequence Homology, Amino Acid; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D029681:Arabidopsis Proteins; D008565:Membrane Proteins; D044763:Ubiquitin-Conjugating Enzymes