title: Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB+1.
abstract: The ubiquitin mutant UBB+1has been identified as a hallmark of neurodegenerative diseases. In this study, we characterize polyubiquitinated forms of UBB+1in vitro and from patient samples. The ability of UBB+1to be readily ubiquitinated by several E2 enzymes provided a mechanism for the controlled synthesis and purification of defined conjugates. This allowed us to utilize polyUb-UBB+1conjugates for biochemical assays, as well as solution NMR. Coupled with our immunoassay for detection of ubiquitinated forms of UBB+1in patient blood samples, we gain a clearer picture of the molecular mechanisms underlying neurodegenerative diseases.
authors.affiliation: Department of Medical Biochemistry, Medical University of Łódź, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Chojnacki
authors.affiliation: Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD, USA.
authors.forename: Daoning
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Adult Psychiatry, Medical University of Łódź, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Talarowska
authors.affiliation: Department of Adult Psychiatry, Medical University of Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gałecki
authors.affiliation: Department of Medical Biochemistry, Medical University of Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Fushman
authors.affiliation: Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Nakasone
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072017:Deubiquitinating Enzymes; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019906:Nuclear Magnetic Resonance, Biomolecular; D025821:Polyubiquitin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D013194:Staining and Labeling; D025801:Ubiquitin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D005452:Fluoresceins; D005456:Fluorescent Dyes; D020033:Protein Isoforms; C486696:STAMBP protein, human; C479419:UBB protein, human; D025801:Ubiquitin; D025821:Polyubiquitin; C037041:fluorescein 5-maleimide; D010450:Endopeptidases; D000072017:Deubiquitinating Enzymes; C538826:OTUB1 protein, human; C000602831:OTUD3 protein, human; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex
keywords: 
  UBB
  +1
  ; biomolecular NMR; deubiquitinase; neurodegeneration; polyubiquitin