Premium
Artificially Linked Ubiquitin Dimers Characterised Structurally and Dynamically by NMR Spectroscopy
Author(s) -
Zhao Xiaohui,
Mißun Maite,
Schneider Tobias,
Müller Franziska,
Lutz Joachim,
Scheffner Martin,
Marx Andreas,
Kovermann Michael
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900146
Subject(s) - dimer , ubiquitin , chemistry , nuclear magnetic resonance spectroscopy , stereochemistry , side chain , covalent bond , biophysics , biochemistry , biology , gene , organic chemistry , polymer
As one of the most prevalent post‐translational modifications in eukaryotic cells, ubiquitylation plays vital roles in many cellular processes, such as protein degradation, DNA metabolism, and cell differentiation. Substrate proteins can be tagged by distinct types of polymeric ubiquitin (Ub) chains, which determine the eventual fate of the modified protein. A facile, click chemistry based approach for the efficient generation of linkage‐defined Ub chains, including Ub dimers, was recently established. Within these chains, individual Ub moieties are connected through a triazole linkage, rather than the natural isopeptide bond. Herein, it is reported that the conformation of an artificially K48‐linked Ub dimer resembles that of the natively linked dimer, with respect to structural and dynamic characteristics, as demonstrated by means of high‐resolution NMR spectroscopy. Thus, it is proposed that artificially linked Ub dimers, as generated by this approach, represent potent tools for studying the inherently different properties and functions of distinct Ub chains.