+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-22650 | ||||||||||||||||||
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タイトル | Cryo-EM structure of STRIPAK complex | ||||||||||||||||||
マップデータ | SK7 primary map | ||||||||||||||||||
試料 |
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キーワード | phosphorylation (リン酸化) / complex / PP2A (プロテインホスファターゼ2) / SIGNALING PROTEIN | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 FAR/SIN/STRIPAK complex / armadillo repeat domain binding / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / MASTL Facilitates Mitotic Progression / mitotic sister chromatid separation / regulation of meiotic cell cycle process involved in oocyte maturation / protein phosphatase type 2A complex ...FAR/SIN/STRIPAK complex / armadillo repeat domain binding / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / MASTL Facilitates Mitotic Progression / mitotic sister chromatid separation / regulation of meiotic cell cycle process involved in oocyte maturation / protein phosphatase type 2A complex / meiotic sister chromatid cohesion, centromeric / peptidyl-serine dephosphorylation / negative regulation of intracellular estrogen receptor signaling pathway / peptidyl-threonine dephosphorylation / positive regulation of microtubule binding / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / female meiotic nuclear division / protein antigen binding / protein phosphatase regulator activity / GABA receptor binding / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Initiation of Nuclear Envelope (NE) Reformation / ERKs are inactivated / negative regulation of epithelial to mesenchymal transition / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / regulation of cell morphogenesis / regulation of growth / Disassembly of the destruction complex and recruitment of AXIN to the membrane / cortical actin cytoskeleton organization / negative regulation of glycolytic process through fructose-6-phosphate / positive regulation of NLRP3 inflammasome complex assembly / Golgi cisterna membrane / myosin phosphatase activity / CTLA4 inhibitory signaling / protein serine/threonine phosphatase activity / Platelet sensitization by LDL / protein-serine/threonine phosphatase / regulation of cell differentiation / ERK/MAPK targets / T cell homeostasis / regulation of G1/S transition of mitotic cell cycle / phosphoprotein phosphatase activity / mesoderm development / chromosome, centromeric region / DARPP-32 events / lateral plasma membrane / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Cyclin A/B1/B2 associated events during G2/M transition / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Resolution of Sister Chromatid Cohesion / cytoskeleton organization / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / protein dephosphorylation / protein phosphatase 2A binding / meiotic cell cycle / protein tyrosine phosphatase activity / chromosome segregation / RHO GTPases Activate Formins / response to lead ion / regulation of protein phosphorylation / Spry regulation of FGF signaling / RAF activation / PKR-mediated signaling / Degradation of beta-catenin by the destruction complex / tau protein binding / positive regulation of protein serine/threonine kinase activity / small GTPase binding / kinase binding / 紡錘体 / Negative regulation of MAPK pathway / Separation of Sister Chromatids / Cyclin D associated events in G1 / microtubule cytoskeleton / Regulation of PLK1 Activity at G2/M Transition / Regulation of TP53 Degradation / response to estradiol / mitotic cell cycle / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / protein-containing complex assembly / 樹状突起スパイン / calmodulin binding / intracellular signal transduction / neuron projection 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | ||||||||||||||||||
データ登録者 | Jeong B-C / Bai XC | ||||||||||||||||||
資金援助 | 米国, 5件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2021 タイトル: Cryo-EM structure of the Hippo signaling integrator human STRIPAK. 著者: Byung-Cheon Jeong / Sung Jun Bae / Lisheng Ni / Xuewu Zhang / Xiao-Chen Bai / Xuelian Luo / 要旨: The striatin-interacting phosphatase and kinase (STRIPAK) complex is a large, multisubunit protein phosphatase 2A (PP2A) assembly that integrates diverse cellular signals in the Hippo pathway to ...The striatin-interacting phosphatase and kinase (STRIPAK) complex is a large, multisubunit protein phosphatase 2A (PP2A) assembly that integrates diverse cellular signals in the Hippo pathway to regulate cell proliferation and survival. The architecture and assembly mechanism of this critical complex are poorly understood. Using cryo-EM, we determine the structure of the human STRIPAK core comprising PP2AA, PP2AC, STRN3, STRIP1, and MOB4 at 3.2-Å resolution. Unlike the canonical trimeric PP2A holoenzyme, STRIPAK contains four copies of STRN3 and one copy of each the PP2AA-C heterodimer, STRIP1, and MOB4. The STRN3 coiled-coil domains form an elongated homotetrameric scaffold that links the complex together. An inositol hexakisphosphate (IP) is identified as a structural cofactor of STRIP1. Mutations of key residues at subunit interfaces disrupt the integrity of STRIPAK, causing aberrant Hippo pathway activation. Thus, STRIPAK is established as a noncanonical PP2A complex with four copies of regulatory STRN3 for enhanced signal integration. | ||||||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_22650.map.gz | 166.2 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-22650-v30.xml emd-22650.xml | 25.4 KB 25.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_22650.png | 348.2 KB | ||
Filedesc metadata | emd-22650.cif.gz | 8.3 KB | ||
その他 | emd_22650_additional_1.map.gz | 166.9 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22650 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22650 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_22650.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | SK7 primary map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.83 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
-追加マップ: Focused map
ファイル | emd_22650_additional_1.map | ||||||||||||
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注釈 | Focused map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : SK7 complex
全体 | 名称: SK7 complex |
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要素 |
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-超分子 #1: SK7 complex
超分子 | 名称: SK7 complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 817.8 KDa |
-分子 #1: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit...
分子 | 名称: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 65.378344 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (バキュロウイルス科) |
配列 | 文字列: MAAADGDDSL YPIAVLIDEL RNEDVQLRLN SIKKLSTIAL ALGVERTRSE LLPFLTDTIY DEDEVLLALA EQLGTFTTLV GGPEYVHCL LPPLESLATV EETVVRDKAV ESLRAISHEH SPSDLEAHFV PLVKRLAGGD WFTSRTSACG LFSVCYPRVS S AVKAELRQ ...文字列: MAAADGDDSL YPIAVLIDEL RNEDVQLRLN SIKKLSTIAL ALGVERTRSE LLPFLTDTIY DEDEVLLALA EQLGTFTTLV GGPEYVHCL LPPLESLATV EETVVRDKAV ESLRAISHEH SPSDLEAHFV PLVKRLAGGD WFTSRTSACG LFSVCYPRVS S AVKAELRQ YFRNLCSDDT PMVRRAAASK LGEFAKVLEL DNVKSEIIPM FSNLASDEQD SVRLLAVEAC VNIAQLLPQE DL EALVMPT LRQAAEDKSW RVRYMVADKF TELQKAVGPE ITKTDLVPAF QNLMKDCEAE VRAAASHKVK EFCENLSADC REN VIMSQI LPCIKELVSD ANQHVKSALA SVIMGLSPIL GKDNTIEHLL PLFLAQLKDE CPEVRLNIIS NLDCVNEVIG IRQL SQSLL PAIVELAEDA KWRVRLAIIE YMPLLAGQLG VEFFDEKLNS LCMAWLVDHV YAIREAATSN LKKLVEKFGK EWAHA TIIP KVLAMSGDPN YLHRMTTLFC INVLSEVCGQ DITTKHMLPT VLRMAGDPVA NVRFNVAKSL QKIGPILDNS TLQSEV KPI LEKLTQDQDV DVKYFAQEAL TVLSLA UniProtKB: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform |
-分子 #2: Striatin-3
分子 | 名称: Striatin-3 / タイプ: protein_or_peptide / ID: 2 / コピー数: 5 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 77.833484 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (バキュロウイルス科) |
配列 | 文字列: MDELAGGGGG GPGMAAPPRQ QQGPGGNLGL SPGGNGAAGG GGPPASEGAG PAAGPELSRP QQYTIPGILH YIQHEWARFE MERAHWEVE RAELQARIAF LQGERKGQEN LKKDLVRRIK MLEYALKQER AKYHKLKYGT ELNQGDLKMP TFESEETKDT E APTAPQNS ...文字列: MDELAGGGGG GPGMAAPPRQ QQGPGGNLGL SPGGNGAAGG GGPPASEGAG PAAGPELSRP QQYTIPGILH YIQHEWARFE MERAHWEVE RAELQARIAF LQGERKGQEN LKKDLVRRIK MLEYALKQER AKYHKLKYGT ELNQGDLKMP TFESEETKDT E APTAPQNS QLTWKQGRQL LRQYLQEVGY TDTILDVRSQ RVRSLLGLSN SEPNGSVETK NLEQILNGGE SPKQKGQEIK RS SGDVLET FNFLENADDS DEDEENDMIE GIPEGKDKHR MNKHKIGNEG LAADLTDDPD TEEALKEFDF LVTAEDGEGA GEA RSSGDG TEWAEPITFP SGGGKSFIMG SDDVLLSVLG LGDLADLTVT NDADYSYDLP ANKDAFRKTW NPKYTLRSHF DGVR ALAFH PVEPVLVTAS EDHTLKLWNL QKTVPAKKSA SLDVEPIYTF RAHIGPVLSL AISSNGEQCF SGGIDATIQW WNMPS PSVD PYDTYEPNVL AGTLVGHTDA VWGLAYSGIK NQLLSCSADG TVRLWNPQEK LPCICTYNGD KKHGIPTSVD FIGCDP AHM VTSFNTGSAV IYDLETSQSL VILSSQVDSG LQSNNHINRV VSHPTLPVTI TAHEDRHIKF FDNKTGKMIH SMVAHLD AV TSLAVDPNGI YLMSGSHDCS IRLWNLDSKT CVQEITAHRK KLDESIYDVA FHSSKAYIAS AGADALAKVF V UniProtKB: Striatin-3 |
-分子 #3: Serine/threonine-protein phosphatase 2A catalytic subunit alpha i...
分子 | 名称: Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO / EC番号: protein-serine/threonine phosphatase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 35.636152 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (バキュロウイルス科) |
配列 | 文字列: MDEKVFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC PVTVCGDVHG QFHDLMELFR IGGKSPDTNY LFMGDYVDR GYYSVETVTL LVALKVRYRE RITILRGNHE SRQITQVYGF YDECLRKYGN ANVWKYFTDL FDYLPLTALV D GQIFCLHG ...文字列: MDEKVFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC PVTVCGDVHG QFHDLMELFR IGGKSPDTNY LFMGDYVDR GYYSVETVTL LVALKVRYRE RITILRGNHE SRQITQVYGF YDECLRKYGN ANVWKYFTDL FDYLPLTALV D GQIFCLHG GLSPSIDTLD HIRALDRLQE VPHEGPMCDL LWSDPDDRGG WGISPRGAGY TFGQDISETF NHANGLTLVS RA HQLVMEG YNWCHDRNVV TIFSAPNYCY RCGNQAAIME LDDTLKYSFL QFDPAPRRGE PHVTRRTPDY FL UniProtKB: Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform |
-分子 #4: MOB-like protein phocein
分子 | 名称: MOB-like protein phocein / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 26.064447 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (バキュロウイルス科) |
配列 | 文字列: MVMAEGTAVL RRNRPGTKAQ DFYNWPDESF DEMDSTLAVQ QYIQQNIRAD CSNIDKILEP PEGQDEGVWK YEHLRQFCLE LNGLAVKLQ SECHPDTCTQ MTATEQWIFL CAAHKTPKEC PAIDYTRHTL DGAACLLNSN KYFPSRVSIK ESSVAKLGSV C RRIYRIFS ...文字列: MVMAEGTAVL RRNRPGTKAQ DFYNWPDESF DEMDSTLAVQ QYIQQNIRAD CSNIDKILEP PEGQDEGVWK YEHLRQFCLE LNGLAVKLQ SECHPDTCTQ MTATEQWIFL CAAHKTPKEC PAIDYTRHTL DGAACLLNSN KYFPSRVSIK ESSVAKLGSV C RRIYRIFS HAYFHHRQIF DEYENETFLC HRFTKFVMKY NLMSKDNLIV PILEEEVQNS VSGESEA UniProtKB: MOB-like protein phocein |
-分子 #5: Striatin-interacting protein 1
分子 | 名称: Striatin-interacting protein 1 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 95.695656 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (バキュロウイルス科) |
配列 | 文字列: MEPAVGGPGP LIVNNKQPQP PPPPPPAAAQ PPPGAPRAAA GLLPGGKARE FNRNQRKDSE GYSESPDLEF EYADTDKWAA ELSELYSYT EGPEFLMNRK CFEEDFRIHV TDKKWTELDT NQHRTHAMRL LDGLEVTARE KRLKVARAIL YVAQGTFGEC S SEAEVQSW ...文字列: MEPAVGGPGP LIVNNKQPQP PPPPPPAAAQ PPPGAPRAAA GLLPGGKARE FNRNQRKDSE GYSESPDLEF EYADTDKWAA ELSELYSYT EGPEFLMNRK CFEEDFRIHV TDKKWTELDT NQHRTHAMRL LDGLEVTARE KRLKVARAIL YVAQGTFGEC S SEAEVQSW MRYNIFLLLE VGTFNALVEL LNMEIDNSAA CSSAVRKPAI SLADSTDLRV LLNIMYLIVE TVHQECEGDK AE WRTMRQT FRAELGSPLY NNEPFAIMLF GMVTKFCSGH APHFPMKKVL LLLWKTVLCT LGGFEELQSM KAEKRSILGL PPL PEDSIK VIRNMRAASP PASASDLIEQ QQKRGRREHK ALIKQDNLDA FNERDPYKAD DSREEEEEND DDNSLEGETF PLER DEVMP PPLQHPQTDR LTCPKGLPWA PKVREKDIEM FLESSRSKFI GYTLGSDTNT VVGLPRPIHE SIKTLKQHKY TSIAE VQAQ MEEEYLRSPL SGGEEEVEQV PAETLYQGLL PSLPQYMIAL LKILLAAAPT SKAKTDSINI LADVLPEEMP TTVLQS MKL GVDVNRHKEV IVKAISAVLL LLLKHFKLNH VYQFEYMAQH LVFANCIPLI LKFFNQNIMS YITAKNSISV LDYPHCV VH ELPELTAESL EAGDSNQFCW RNLFSCINLL RILNKLTKWK HSRTMMLVVF KSAPILKRAL KVKQAMMQLY VLKLLKVQ T KYLGRQWRKS NMKTMSAIYQ KVRHRLNDDW AYGNDLDARP WDFQAEECAL RANIERFNAR RYDRAHSNPD FLPVDNCLQ SVLGQRVDLP EDFQMNYDLW LEREVFSKPI SWEELLQ UniProtKB: Striatin-interacting protein 1 |
-分子 #6: MANGANESE (II) ION
分子 | 名称: MANGANESE (II) ION / タイプ: ligand / ID: 6 / コピー数: 2 / 式: MN |
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分子量 | 理論値: 54.938 Da |
-分子 #7: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 7 / コピー数: 2 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-分子 #8: INOSITOL HEXAKISPHOSPHATE
分子 | 名称: INOSITOL HEXAKISPHOSPHATE / タイプ: ligand / ID: 8 / コピー数: 1 / 式: IHP |
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分子量 | 理論値: 660.035 Da |
Chemical component information | ChemComp-IHP: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 2.0 mg/mL | ||||||||||||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 80 sec. / 前処理 - 雰囲気: AIR / 詳細: The grid was coated with gold prior to use | ||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 70.0 µm / 倍率(補正後): 59524 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 検出モード: SUPER-RESOLUTION / 実像数: 4356 / 平均電子線量: 64.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
粒子像選択 | 選択した数: 2451582 |
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初期モデル | モデルのタイプ: PDB ENTRY / 詳細: PDB ID 2NPP, 4N6J, 2YMU, 5YF4 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 3次元分類 | ソフトウェア - 名称: RELION (ver. 3) |
最終 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: RELION (ver. 3) |
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 3) / 使用した粒子像数: 87779 |
-原子モデル構築 1
初期モデル |
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精密化 | 空間: REAL / プロトコル: AB INITIO MODEL | ||||||||||
得られたモデル | PDB-7k36: |