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Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB+1.


ABSTRACT: The ubiquitin mutant UBB+1 has been identified as a hallmark of neurodegenerative diseases. In this study, we characterize polyubiquitinated forms of UBB+1 in vitro and from patient samples. The ability of UBB+1 to 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+1 conjugates for biochemical assays, as well as solution NMR. Coupled with our immunoassay for detection of ubiquitinated forms of UBB+1 in patient blood samples, we gain a clearer picture of the molecular mechanisms underlying neurodegenerative diseases.

SUBMITTER: Chojnacki M 

PROVIDER: S-EPMC5182158 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB<sup>+1</sup>.

Chojnacki Michal M   Zhang Daoning D   Talarowska Monika M   Gałecki Piotr P   Szemraj Janusz J   Fushman David D   Nakasone Mark A MA  

FEBS letters 20161122 24


The ubiquitin mutant UBB<sup>+1</sup> has been identified as a hallmark of neurodegenerative diseases. In this study, we characterize polyubiquitinated forms of UBB<sup>+1</sup> in vitro and from patient samples. The ability of UBB<sup>+1</sup> to 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<sup>+1</sup> conjugates for biochemical assays, as well as solution NMR. Coup  ...[more]

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