R-catcher, a potent molecular tool to unveil the arginylome

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Title
R-catcher, a potent molecular tool to unveil the arginylome
Author(s)
Taewook Seo; Jihyo Kim; Ho Chul Shin; Jung Gi Kim; S Ju; L Nawale; Goeun Han; Hye Seon Lee; G Bang; J Y Kim; J K Bang; Kyung Ho LeeNak-Kyun SoungJoonsung Hwang; C Lee; Seung Jun KimBo Yeon KimHyunjoo Cha-Molstad
Bibliographic Citation
Cellular and Molecular Life Sciences, vol. 78, no. 7, pp. 3725-3741
Publication Year
2021
Abstract
Protein arginylation is a critical regulator of a variety of biological processes. The ability to uncover the global arginylation pattern and its associated signaling pathways would enable us to identify novel disease targets. Here, we report the development of a tool able to capture the N-terminal arginylome. This tool, termed R-catcher, is based on the ZZ domain of p62, which was previously shown to bind N-terminally arginylated proteins. Mutating the ZZ domain enhanced its binding specificity and affinity for Nt-Arg. R-catcher pulldown coupled to LC-MS/MS led to the identification of 59 known and putative arginylated proteins. Among these were a subgroup of novel ATE1-dependent arginylated ER proteins that are linked to diverse biological pathways, including cellular senescence and vesicle-mediated transport as well as diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer's disease. This study presents the first molecular tool that allows the unbiased identification of arginylated proteins, thereby unlocking the arginylome and provide a new path to disease biomarker discovery.
Keyword
ATE1 R-transferaseBaitFBLN1CLUSSERPINH1PRDX4Unfolded Protein ResponseExtracellular exosomeInnate Immune SystemProstate cancerOvarian cancer
ISSN
1420-682X
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s00018-021-03805-x
Type
Article
Appears in Collections:
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
Ochang Branch Institute > Nucleic Acid Therapeutics Research Center > 1. Journal Articles
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