title: Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state.
abstract: 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.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morito
authors.affiliation: Cellular and Structural Physiology Institute, Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: 1] Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, 606-8502, Japan [2] Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hoseki
authors.affiliation: Laboratory of Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kitamura
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kotani
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kiso
authors.affiliation: Laboratory of Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kinjo
authors.affiliation: Cellular and Structural Physiology Institute, Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiyoshi
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D009072:Moyamoya Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011487:Protein Conformation; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases