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Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB +1
Author(s) -
Chojnacki Michal,
Zhang Daoning,
Talarowska Monika,
Gałecki Piotr,
Szemraj Janusz,
Fushman David,
Nakasone Mark A.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12484
Subject(s) - ubiquitin , mutant , in vitro , chemistry , biochemistry , gene
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.