- EMDB-20814: Cryo-EM structure of the FLCN-FNIP2-Rag-Ragulator complex -
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基本情報
登録情報
データベース: EMDB / ID: EMD-20814
タイトル
Cryo-EM structure of the FLCN-FNIP2-Rag-Ragulator complex
マップデータ
試料
複合体: Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases and the scaffolding protein complex Ragulator
タンパク質・ペプチド: x 9種
リガンド: x 3種
機能・相同性
機能・相同性情報
negative regulation of cell proliferation involved in kidney development / negative regulation of post-translational protein modification / cell proliferation involved in kidney development / regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / FNIP-folliculin RagC/D GAP ...negative regulation of cell proliferation involved in kidney development / negative regulation of post-translational protein modification / cell proliferation involved in kidney development / regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding / FNIP-folliculin RagC/D GAP / Ragulator complex / negative regulation of brown fat cell differentiation / regulation of Ras protein signal transduction / protein localization to cell junction / regulation of TORC1 signaling / negative regulation of lysosome organization / regulation of pro-B cell differentiation / protein localization to lysosome / regulation of TOR signaling / TORC1 signaling / endosome organization / fibroblast migration / MTOR signalling / Amino acids regulate mTORC1 / lysosome localization / ATPase inhibitor activity / Energy dependent regulation of mTOR by LKB1-AMPK / kinase activator activity / protein localization to membrane / negative regulation of TOR signaling / enzyme inhibitor activity / enzyme-substrate adaptor activity / negative regulation of glycolytic process / cell-cell junction assembly / negative regulation of cold-induced thermogenesis / negative regulation of Rho protein signal transduction / azurophil granule membrane / endosomal transport / regulation of cell size / small GTPase-mediated signal transduction / Macroautophagy / lysosome organization / positive regulation of transforming growth factor beta receptor signaling pathway / RHOJ GTPase cycle / RHOQ GTPase cycle / mTORC1-mediated signalling / tertiary granule membrane / CDC42 GTPase cycle / hemopoiesis / ficolin-1-rich granule membrane / RHOH GTPase cycle / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / centriolar satellite / RHOG GTPase cycle / TOR signaling / regulation of receptor recycling / positive regulation of TOR signaling / RAC2 GTPase cycle / RAC3 GTPase cycle / response to amino acid / cellular response to nutrient levels / positive regulation of autophagy / specific granule membrane / positive regulation of intrinsic apoptotic signaling pathway / protein-membrane adaptor activity / energy homeostasis / epithelial cell proliferation / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / RAC1 GTPase cycle / positive regulation of TORC1 signaling / ERK1 and ERK2 cascade / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to starvation / cellular response to amino acid starvation / intrinsic apoptotic signaling pathway / GTPase activator activity / viral genome replication / negative regulation of autophagy / cellular response to amino acid stimulus / transforming growth factor beta receptor signaling pathway / RNA splicing / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / guanyl-nucleotide exchange factor activity / cholesterol homeostasis / positive regulation of interleukin-8 production / regulation of cell growth / TP53 Regulates Metabolic Genes / phosphoprotein binding / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / regulation of protein phosphorylation / response to virus / MAP2K and MAPK activation / positive regulation of protein-containing complex assembly / cilium / negative regulation of ERK1 and ERK2 cascade / mitotic spindle / positive regulation of protein localization to nucleus / GDP binding / negative regulation of epithelial cell proliferation 類似検索 - 分子機能
Folliculin / Folliculin, DENN domain / Folliculin, DENN domain, C-terminal superfamily / Folliculin C-terminal domain / Folliculin-interacting protein family / Folliculin-interacting protein, N-terminal domain / Folliculin-interacting protein, middle domain / Folliculin-interacting protein, C-terminal domain / Folliculin-interacting protein N-terminus / Folliculin-interacting protein middle domain ...Folliculin / Folliculin, DENN domain / Folliculin, DENN domain, C-terminal superfamily / Folliculin C-terminal domain / Folliculin-interacting protein family / Folliculin-interacting protein, N-terminal domain / Folliculin-interacting protein, middle domain / Folliculin-interacting protein, C-terminal domain / Folliculin-interacting protein N-terminus / Folliculin-interacting protein middle domain / Folliculin-interacting protein C-terminus / Tripartite DENN domain, FNIP1/2-type / Tripartite DENN FNIP1/2-type domain profile. / Folliculin/SMCR8, longin domain / Folliculin/SMCR8, tripartite DENN domain / Vesicle coat protein involved in Golgi to plasma membrane transport / Tripartite DENN FLCN/SMCR8-type domain profile. / LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / RagA/B / Mitogen-activated protein kinase kinase 1 interacting / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / Gtr1/RagA G protein / RagC/D / Gtr1/RagA G protein conserved region / Ragulator complex protein LAMTOR2-like / Roadblock/LAMTOR2 domain / Roadblock/LC7 domain / Roadblock/LC7 domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Ragulator complex protein LAMTOR5 / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR1 / Ras-related GTP-binding protein A / Folliculin / Ras-related GTP-binding protein C / Folliculin-interacting protein 2 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR2 類似検索 - 構成要素
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01 CA103866
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
R37 AI47389
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01 CA129105
米国
Lustgarten Foundation
米国
Department of Defense (DOD, United States)
W81XWH-15-1-0230
米国
Tuberous Sclerosis Association
米国
Howard Hughes Medical Institute (HHMI)
米国
引用
ジャーナル: Cell / 年: 2019 タイトル: Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex. 著者: Kuang Shen / Kacper B Rogala / Hui-Ting Chou / Rick K Huang / Zhiheng Yu / David M Sabatini / 要旨: mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN- ...mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway.
ダウンロード / ファイル: emd_20814.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
ボクセルのサイズ
X=Y=Z: 1.04 Å
密度
表面レベル
登録者による: 0.002 / ムービー #1: 0.02
最小 - 最大
-0.058811273 - 0.10569042
平均 (標準偏差)
0.000012088260 (±0.0023958504)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
360
360
360
Spacing
360
360
360
セル
A=B=C: 374.4 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.04
1.04
1.04
M x/y/z
360
360
360
origin x/y/z
0.000
0.000
0.000
length x/y/z
374.400
374.400
374.400
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
92
92
62
NX/NY/NZ
290
290
360
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
360
360
360
D min/max/mean
-0.059
0.106
0.000
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添付データ
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試料の構成要素
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全体 : Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases an...
全体
名称: Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases and the scaffolding protein complex Ragulator
要素
複合体: Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases and the scaffolding protein complex Ragulator
タンパク質・ペプチド: Folliculin
タンパク質・ペプチド: Ragulator complex protein LAMTOR3
タンパク質・ペプチド: Ragulator complex protein LAMTOR2
タンパク質・ペプチド: Ragulator complex protein LAMTOR5
タンパク質・ペプチド: Ragulator complex protein LAMTOR4
タンパク質・ペプチド: Ragulator complex protein LAMTOR1
タンパク質・ペプチド: Ras-related GTP-binding protein A
タンパク質・ペプチド: Ras-related GTP-binding protein C
タンパク質・ペプチド: Folliculin-interacting protein 2
リガンド: GUANOSINE-5'-DIPHOSPHATE
リガンド: PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER
リガンド: MAGNESIUM ION
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超分子 #1: Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases an...
超分子
名称: Nonameric complex of FLCN-FNIP2 with its substrate Rag GTPases and the scaffolding protein complex Ragulator タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#9