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基本情報
登録情報 | データベース: EMDB / ID: EMD-30708 | |||||||||
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タイトル | Cryo-EM structure of human TSC complex | |||||||||
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![]() | TSC complex / Regulator of cell growth / GTPase-activating protein / Elongated arch-shaped fold / GENE REGULATION | |||||||||
機能・相同性 | ![]() memory T cell differentiation / : / TSC1-TSC2 complex / Inhibition of TSC complex formation by PKB / : / cellular response to decreased oxygen levels / regulation of insulin receptor signaling pathway / negative regulation of cilium assembly / regulation of cell-matrix adhesion / ATPase inhibitor activity ...memory T cell differentiation / : / TSC1-TSC2 complex / Inhibition of TSC complex formation by PKB / : / cellular response to decreased oxygen levels / regulation of insulin receptor signaling pathway / negative regulation of cilium assembly / regulation of cell-matrix adhesion / ATPase inhibitor activity / cardiac muscle cell differentiation / negative regulation of ATP-dependent activity / cell projection organization / Energy dependent regulation of mTOR by LKB1-AMPK / response to growth factor / negative regulation of cell size / regulation of stress fiber assembly / activation of GTPase activity / protein folding chaperone complex / anoikis / negative regulation of TOR signaling / TBC/RABGAPs / negative regulation of mitophagy / regulation of small GTPase mediated signal transduction / AKT phosphorylates targets in the cytosol / negative regulation of macroautophagy / Macroautophagy / positive chemotaxis / negative regulation of Wnt signaling pathway / glucose import / Constitutive Signaling by AKT1 E17K in Cancer / positive regulation of focal adhesion assembly / associative learning / regulation of endocytosis / positive regulation of macroautophagy / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / phosphatase binding / ribosomal subunit export from nucleus / vesicle-mediated transport / negative regulation of insulin receptor signaling pathway / negative regulation of TORC1 signaling / Hsp70 protein binding / myelination / viral process / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to starvation / GTPase activator activity / lipid droplet / adult locomotory behavior / cell-matrix adhesion / insulin-like growth factor receptor signaling pathway / ciliary basal body / positive regulation of GTPase activity / positive regulation of protein ubiquitination / kidney development / neural tube closure / hippocampus development / TP53 Regulates Metabolic Genes / synapse organization / negative regulation of protein kinase activity / Hsp90 protein binding / response to insulin / potassium ion transport / cerebral cortex development / small GTPase binding / endocytosis / protein import into nucleus / protein localization / lamellipodium / regulation of translation / heart development / protein-folding chaperone binding / cell cortex / cytoplasmic vesicle / adaptive immune response / cell population proliferation / postsynaptic density / lysosome / protein stabilization / regulation of cell cycle / negative regulation of translation / negative regulation of cell population proliferation / lysosomal membrane / perinuclear region of cytoplasm / Golgi apparatus / protein homodimerization activity / protein-containing complex / membrane / nucleus / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.4 Å | |||||||||
![]() | Yang H / Yu Z / Chen X / Li J / Li N / Cheng J / Gao N / Yuan H / Ye D / Guan K / Xu Y | |||||||||
![]() | ![]() タイトル: Structural insights into TSC complex assembly and GAP activity on Rheb. 著者: Huirong Yang / Zishuo Yu / Xizi Chen / Jiabei Li / Ningning Li / Jiaxuan Cheng / Ning Gao / Hai-Xin Yuan / Dan Ye / Kun-Liang Guan / Yanhui Xu / ![]() ![]() 要旨: Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small ...Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity. | |||||||||
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 501.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 17 KB 17 KB | 表示 表示 | ![]() |
画像 | ![]() | 19.3 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.356 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : Cryo-EM structure of human TSC complex
全体 | 名称: Cryo-EM structure of human TSC complex |
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要素 |
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-超分子 #1: Cryo-EM structure of human TSC complex
超分子 | 名称: Cryo-EM structure of human TSC complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
-分子 #1: Hamartin
分子 | 名称: Hamartin / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 129.945367 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL ETSSQPALHI LTTLQEPHDK HLLDRINEYV GKAATRLSI LSLLGHVIRL QPSWKHKLSQ APLLPSLLKC LKMDTDVVVL TTGVLVLITM LPMIPQSGKQ HLLDFFDIFG R LSSWCLKK ...文字列: MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL ETSSQPALHI LTTLQEPHDK HLLDRINEYV GKAATRLSI LSLLGHVIRL QPSWKHKLSQ APLLPSLLKC LKMDTDVVVL TTGVLVLITM LPMIPQSGKQ HLLDFFDIFG R LSSWCLKK PGHVAEVYLV HLHASVYALF HRLYGMYPCN FVSFLRSHYS MKENLETFEE VVKPMMEHVR IHPELVTGSK DH ELDPRRW KRLETHDVVI ECAKISLDPT EASYEDGYSV SHQISARFPH RSADVTTSPY ADTQNSYGCA TSTPYSTSRL MLL NMPGQL PQTLSSPSTR LITEPPQATL WSPSMVCGMT TPPTSPGNVP PDLSHPYSKV FGTTAGGKGT PLGTPATSPP PAPL CHSDD YVHISLPQAT VTPPRKEERM DSARPCLHRQ HHLLNDRGSE EPPGSKGSVT LSDLPGFLGD LASEEDSIEK DKEEA AISR ELSEITTAEA EPVVPRGGFD SPFYRDSLPG SQRKTHSAAS SSQGASVNPE PLHSSLDKLG PDTPKQAFTP IDLPCG SAD ESPAGDRECQ TSLETSIFTP SPCKIPPPTR VGFGSGQPPP YDHLFEVALP KTAHHFVIRK TEELLKKAKG NTEEDGV PS TSPMEVLDRL IQQGADAHSK ELNKLPLPSK SVDWTHFGGS PPSDEIRTLR DQLLLLHNQL LYERFKRQQH ALRNRRLL R KVIKAAALEE HNAAMKDQLK LQEKDIQMWK VSLQKEQARY NQLQEQRDTM VTKLHSQIRQ LQHDREEFYN QSQELQTKL EDCRNMIAEL RIELKKANNK VCHTELLLSQ VSQKLSNSES VQQQMEFLNR QLLVLGEVNE LYLEQLQNKH SDTTKEVEMM KAAYRKELE KNRSHVLQQT QRLDTSQKRI LELESHLAKK DHLLLEQKKY LEDVKLQARG QLQAAESRYE AQKRITQVFE L EILDLYGR LEKDGLLKKL EEEKAEAAEA AEERLDCCND GCSDSMVGHN EEASGHNGET KTPRPSSARG SSGSRGGGGS SS SSSELST PEKPPHQRAG PFSSRWETTM GEASASIPTT VGSLPSSKSF LGMKARELFR NKSESQCDED GMTSSLSESL KTE LGKDLG VEAKIPLNLD GPHPSPPTPD SVGQLHIMDY NETHHEHS UniProtKB: Hamartin |
-分子 #2: Isoform 7 of Tuberin
分子 | 名称: Isoform 7 of Tuberin / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 188.182312 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MECGLNNRIR MIGQICEVAK TKKFEEHAVE ALWKAVADLL QPERPLEARH AVLALLKAIV QGQGERLGVL RALFFKVIKD YPSNEDLHE RLEVFKALTD NGRHITYLEE ELADFVLQWM DVGLSSEFLL VLVNLVKFNS CYLDEYIARM VQMICLLCVR T ASSVDIEV ...文字列: MECGLNNRIR MIGQICEVAK TKKFEEHAVE ALWKAVADLL QPERPLEARH AVLALLKAIV QGQGERLGVL RALFFKVIKD YPSNEDLHE RLEVFKALTD NGRHITYLEE ELADFVLQWM DVGLSSEFLL VLVNLVKFNS CYLDEYIARM VQMICLLCVR T ASSVDIEV SLQVLDAVVC YNCLPAESLP LFIVTLCRTI NVKELCEPCW KLMRNLLGTH LGHSAIYNMC HLMEDRAYME DA PLLRGAV FFVGMALWGA HRLYSLRNSP TSVLPSFYQA MACPNEVVSY EIVLSITRLI KKYRKELQVV AWDILLNIIE RLL QQLQTL DSPELRTIVH DLLTTVEELC DQNEFHGSQE RYFELVERCA DQRPESSLLN LISYRAQSIH PAKDGWIQNL QALM ERFFR SESRGAVRIK VLDVLSFVLL INRQFYEEEL INSVVISQLS HIPEDKDHQV RKLATQLLVD LAEGCHTHHF NSLLD IIEK VMARSLSPPP ELEERDVAAY SASLEDVKTA VLGLLVILQT KLYTLPASHA TRVYEMLVSH IQLHYKHSYT LPIASS IRL QAFDFLLLLR ADSLHRLGLP NKDGVVRFSP YCVCDYMEPE RGSEKKTSGP LSPPTGPPGP APAGPAVRLG SVPYSLL FR VLLQCLKQES DWKVLKLVLG RLPESLRYKV LIFTSPCSVD QLCSALCSML SGPKTLERLR GAPEGFSRTD LHLAVVPV L TALISYHNYL DKTKQREMVY CLEQGLIHRC ASQCVVALSI CSVEMPDIII KALPVLVVKL THISATASMA VPLLEFLST LARLPHLYRN FAAEQYASVF AISLPYTNPS KFNQYIVCLA HHVIAMWFIR CRLPFRKDFV PFITKGLRSN VLLSFDDTPE KDSFRARST SLNERPKSRI QTSLTSASLG SADENSVAQA DDSLKNLHLE LTETCLDMMA RYVFSNFTAV PKRSPVGEFL L AGGRTKTW LVGNKLVTVT TSVGTGTRSL LGLDSGELQS GPESSSSPGV HVRQTKEAPA KLESQAGQQV SRGARDRVRS MS GGHGLRV GALDVPASQF LGSATSPGPR TAPAAKPEKA SAGTRVPVQE KTNLAAYVPL LTQGWAEILV RRPTGNTSWL MSL ENPLSP FSSDINNMPL QELSNALMAA ERFKEHRDTA LYKSLSVPAA STAKPPPLPR SNTDSAVVME EGSPGEVPVL VEPP GLEDV EAALGMDRRT DAYSRSSSVS SQEEKSLHAE ELVGRGIPIE RVVSSEGGRP SVDLSFQPSQ PLSKSSSSPE LQTLQ DILG DPGDKADVGR LSPEVKARSQ SGTLDGESAA WSASGEDSRG QPEGPLPSSS PRSPSGLRPR GYTISDSAPS RRGKRV ERD ALKSRATASN AEKVPGINPS FVFLQLYHSP FFGDESNKPI LLPNESQSFE RSVQLLDQIP SYDTHKIAVL YVGEGQS NS ELAILSNEHG SYRYTEFLTG LGRLIELKDC QPDKVYLGGL DVCGEDGQFT YCWHDDIMQA VFHIATLMPT KDVDKHRC D KKRHLGNDFV SIVYNDSGED FKLGTIKGQF NFVHVIVTPL DYECNLVSLQ CRKDMEGLVD TSVAKIVSDR NLPFVARQM ALHANMASQV HHSRSNPTDI YPSKWIARLR HIKRLRQRIC EEAAYSNPSL PLVHPPSHSK APAQTPAEPT PGYEVGQRKR LISSVEDFT EFV UniProtKB: Tuberin |
-分子 #3: TBC1 domain family member 7
分子 | 名称: TBC1 domain family member 7 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 30.911129 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: GVEEKKSLEI LLKDDRLDTE KLCTFSQRFP LPSMYRALVW KVLLGILPPH HESHAKVMMY RKEQYLDVLH ALKVVRFVSD ATPQAEVYL RMYQLESGKL PRSPSFPLEP DDEVFLAIAK AMEEMVEDSV DCYWITRRFV NQLNTKYRDS LPQLPKAFEQ Y LNLEDGRL ...文字列: GVEEKKSLEI LLKDDRLDTE KLCTFSQRFP LPSMYRALVW KVLLGILPPH HESHAKVMMY RKEQYLDVLH ALKVVRFVSD ATPQAEVYL RMYQLESGKL PRSPSFPLEP DDEVFLAIAK AMEEMVEDSV DCYWITRRFV NQLNTKYRDS LPQLPKAFEQ Y LNLEDGRL LTHLRMCSAA PKLPYDLWFK RCFAGCLPES SLQRVWDKVV SGSCKILVFV AVEILLTFKI KVMALNSAEK IT KFLENIP QDSSDAIVSK AIDLWHKHCG UniProtKB: TBC1 domain family member 7 |
-分子 #4: unknown protein
分子 | 名称: unknown protein / タイプ: protein_or_peptide / ID: 4 詳細: The author does not know what chain F is derived from. コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 22.230297 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) ...文字列: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK) |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 131022 |
初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |