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Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and u...

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Autores principales: Morito, Daisuke, Nishikawa, Kouki, Hoseki, Jun, Kitamura, Akira, Kotani, Yuri, Kiso, Kazumi, Kinjo, Masataka, Fujiyoshi, Yoshinori, Nagata, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963067/
https://www.ncbi.nlm.nih.gov/pubmed/24658080
http://dx.doi.org/10.1038/srep04442
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author Morito, Daisuke
Nishikawa, Kouki
Hoseki, Jun
Kitamura, Akira
Kotani, Yuri
Kiso, Kazumi
Kinjo, Masataka
Fujiyoshi, Yoshinori
Nagata, Kazuhiro
author_facet Morito, Daisuke
Nishikawa, Kouki
Hoseki, Jun
Kitamura, Akira
Kotani, Yuri
Kiso, Kazumi
Kinjo, Masataka
Fujiyoshi, Yoshinori
Nagata, Kazuhiro
author_sort Morito, Daisuke
collection PubMed
description Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.
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spelling pubmed-39630672014-03-25 Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state Morito, Daisuke Nishikawa, Kouki Hoseki, Jun Kitamura, Akira Kotani, Yuri Kiso, Kazumi Kinjo, Masataka Fujiyoshi, Yoshinori Nagata, Kazuhiro Sci Rep Article Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. Nature Publishing Group 2014-03-24 /pmc/articles/PMC3963067/ /pubmed/24658080 http://dx.doi.org/10.1038/srep04442 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
spellingShingle Article
Morito, Daisuke
Nishikawa, Kouki
Hoseki, Jun
Kitamura, Akira
Kotani, Yuri
Kiso, Kazumi
Kinjo, Masataka
Fujiyoshi, Yoshinori
Nagata, Kazuhiro
Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state
title Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state
title_full Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state
title_fullStr Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state
title_full_unstemmed Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state
title_short Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state
title_sort moyamoya disease-associated protein mysterin/rnf213 is a novel aaa+ atpase, which dynamically changes its oligomeric state
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963067/
https://www.ncbi.nlm.nih.gov/pubmed/24658080
http://dx.doi.org/10.1038/srep04442
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