2024-03-29T11:53:41Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/861692022-11-17T02:08:08Zhdl_2115_20055hdl_2115_8527Conformational stabilization of optineurin by the dynamic interaction of linear polyubiquitin1000010580152Kitamura, AkiraNumazawa, Rika1000070177971Kinjo, Masatakaopen access©2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution 4.0 InternationalOptineurinRab8LC3ALSPolyubiquitinProtein aggregationFCCS490Optineurin produces intracellular multi-functions involving autophagy, vesicular trafficking, and negative regulation of inflammation signaling through interaction with various proteins such as ATG8/LC3, Rab8, and polyubiquitin. Optineurin is a component of cytoplasmic inclusion bodies (IBs) in motor neurons from amyotrophic lateral sclerosis (ALS), and its mutation E478G, has been identified in patients with ALS. However, the mechanism by which polyubiquitin binding modulates the interaction partners of OPTN and ALS-associated IB formation is still unclear. To address this issue, we analyzed the interaction of Optineurin with Rab8 and LC3 in the absence and presence of linear polyubiquitin chains using fluorescence cross-correlation spectroscopy and IB formation efficiency of the E478G mutant of Optineurin during Rab8 depletion using fluorescence microscopy. Here, we hypothesize that linear polyubiquitin binding to Optineurin dynamically induces LC3 association and Rab8 dissociation, likely through a conformational change of Optineurin, and the dynamic conformational change may prevent the aggregate formation of mutant Optineurin.Elsevier2021-06-25engjournal articleAMhttp://hdl.handle.net/2115/86169https://doi.org/10.1016/j.bbrc.2021.04.1030006-291XAA00564395Biochemical and Biophysical Research Communications559203209https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/86169/1/Biochem.Biophys.Res.Commun._559.pdfapplication/pdf174.31 KB2021-06-25