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データを開く
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基本情報
登録情報 | データベース: SASBDB / ID: SASDCB2 |
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![]() | Rab family protein CtRoc-COR nucleotide free
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機能・相同性 | ![]() |
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![]() | ![]() タイトル: A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover. 著者: Egon Deyaert / Lina Wauters / Giambattista Guaitoli / Albert Konijnenberg / Margaux Leemans / Susanne Terheyden / Arsen Petrovic / Rodrigo Gallardo / Laura M Nederveen-Schippers / Panagiotis ...著者: Egon Deyaert / Lina Wauters / Giambattista Guaitoli / Albert Konijnenberg / Margaux Leemans / Susanne Terheyden / Arsen Petrovic / Rodrigo Gallardo / Laura M Nederveen-Schippers / Panagiotis S Athanasopoulos / Henderikus Pots / Peter J M Van Haastert / Frank Sobott / Christian Johannes Gloeckner / Rouslan Efremov / Arjan Kortholt / Wim Versées / ![]() ![]() ![]() ![]() 要旨: Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 ...Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is regulated. Here, we show that oligomerization of a homologous bacterial Roco protein depends on the nucleotide load. The protein is mainly dimeric in the nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding, leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD-associated mutation stabilizes the dimer and decreases the GTPase activity. This work thus provides insights into the conformational cycle of Roco proteins and suggests a link between oligomerization and disease-associated mutations in LRRK2. |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
-モデル
モデル #1163 | ![]() タイプ: dummy / ソフトウェア: (5.3) / ダミー原子の半径: 3.25 A / 対称性: P2 / カイ2乗値: 0.797 ![]() |
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モデル #1164 | ![]() タイプ: mix / ダミー原子の半径: 1.90 A / 対称性: P2 / カイ2乗値: 0.896 ![]() |
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試料
![]() | 名称: Rab family protein CtRoc-COR nucleotide free / 試料濃度: 1.00-2.00 |
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バッファ | 名称: 20 mM HEPES 150 mM NaCl 5 mM MgCl2 5% Glycerol 1 mM DTT pH: 7.5 |
要素 #605 | タイプ: protein / 記述: Rab family protein / 分子量: 64.865 / 分子数: 2 由来: Chlorobium tepidum (strain ATCC 49652 / DSM 12025 / NBRC 103806 / TLS) 参照: UniProt: Q8KC98_CHL 配列: MSYYHHHHHH DYDIPTTENL YFQGAMGSDN PLESPPPEIV KQGKEAVRQY FQSIEEARSK GEALVHLQEI KVHLIGDGMA GKTSLLKQLI GETFDPKESQ THGLNVVTKQ APNIKGLEND DELKECLFHF WDFGGQEIMH ASHQFFMTRS SVYMLLLDSR TDSNKHYWLR ...配列: MSYYHHHHHH DYDIPTTENL YFQGAMGSDN PLESPPPEIV KQGKEAVRQY FQSIEEARSK GEALVHLQEI KVHLIGDGMA GKTSLLKQLI GETFDPKESQ THGLNVVTKQ APNIKGLEND DELKECLFHF WDFGGQEIMH ASHQFFMTRS SVYMLLLDSR TDSNKHYWLR HIEKYGGKSP VIVVMNKIDE NPSYNIEQKK INERFPAIEN RFHRISCKNG DGVESIAKSL KSAVLHPDSI YGTPLAPSWI KVKEKLVEAT TAQRYLNRTE VEKICNDSGI TDPGERKTLL GYLNNLGIVL YFEALDLSEI YVLDPHWVTI GVYRIINSSK TKNGHLNTSA LGYILNEEQI RCDEYDPAKN NKFTYTLLEQ RYLLDIMKQF ELCYDEGKGL FIIPSNLPTQ IDNEPEITEG EPLRFIMKYD YLPSTIIPRL MIAMQHQILD RMQWRYGMVL KSQDHEGALA KVVAETKDST ITIAIQGEPR CKREYLSIIW YEIKKINANF TNLDVKEFIP LPGHPDELVE YKELLGLEKM GRDEYVSGKL EKVFSVSKML DSVISKEERN KER |
-実験情報
ビーム | 設備名称: SOLEIL SWING ![]() ![]() | |||||||||||||||||||||||||||||||||
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検出器 | 名称: AVIEX / タイプ: CCD | |||||||||||||||||||||||||||||||||
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距離分布関数 P(R) |
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結果 |
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