+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-20552 | |||||||||
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タイトル | Structure of a MAPK pathway complex | |||||||||
マップデータ | Structure of a MAPK pathway complex | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / trehalose metabolism in response to stress / regulation of axon regeneration / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / mitogen-activated protein kinase kinase / negative regulation of synaptic vesicle exocytosis / labyrinthine layer development ...epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / CD4-positive, alpha-beta T cell differentiation / placenta blood vessel development / trehalose metabolism in response to stress / regulation of axon regeneration / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / mitogen-activated protein kinase kinase / negative regulation of synaptic vesicle exocytosis / labyrinthine layer development / MAP-kinase scaffold activity / type B pancreatic cell proliferation / Signalling to p38 via RIT and RIN / cerebellar cortex formation / head morphogenesis / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / endothelial cell apoptotic process / Signaling by MAP2K mutants / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / regulation of Golgi inheritance / mitogen-activated protein kinase kinase binding / trachea formation / regulation of T cell differentiation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / positive regulation of axonogenesis / regulation of stress-activated MAPK cascade / Frs2-mediated activation / ERBB2-ERBB3 signaling pathway / stress fiber assembly / positive regulation of axon regeneration / protein kinase activator activity / endodermal cell differentiation / face development / MAPK3 (ERK1) activation / synaptic vesicle exocytosis / somatic stem cell population maintenance / Bergmann glial cell differentiation / MAP kinase kinase activity / thyroid gland development / Uptake and function of anthrax toxins / MAP kinase kinase kinase activity / Schwann cell development / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / keratinocyte differentiation / positive regulation of stress fiber assembly / response to cAMP / cellular response to calcium ion / ERK1 and ERK2 cascade / myelination / protein serine/threonine/tyrosine kinase activity / protein serine/threonine kinase activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / substrate adhesion-dependent cell spreading / insulin-like growth factor receptor signaling pathway / cellular response to nerve growth factor stimulus / thymus development / Signal transduction by L1 / cell motility / long-term synaptic potentiation / animal organ morphogenesis / RAF activation / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / visual learning / MAP2K and MAPK activation / positive regulation of protein serine/threonine kinase activity / neuron differentiation / epidermal growth factor receptor signaling pathway / response to peptide hormone / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / chemotaxis / MAPK cascade / cellular senescence / Signaling by BRAF and RAF1 fusions / cellular response to xenobiotic stimulus / late endosome / presynapse / positive regulation of peptidyl-serine phosphorylation / heart development / T cell receptor signaling pathway / regulation of cell population proliferation / cell body / T cell differentiation in thymus / scaffold protein binding / protein tyrosine kinase activity / negative regulation of neuron apoptotic process / Ras protein signal transduction / positive regulation of ERK1 and ERK2 cascade / early endosome 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Beet armyworm (シロイチモジヨトウ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 5.7 Å | |||||||||
データ登録者 | Park E / Rawson S / Jeon H / Eck MJ | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nature / 年: 2019 タイトル: Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. 著者: Eunyoung Park / Shaun Rawson / Kunhua Li / Byeong-Won Kim / Scott B Ficarro / Gonzalo Gonzalez-Del Pino / Humayun Sharif / Jarrod A Marto / Hyesung Jeon / Michael J Eck / 要旨: RAF family kinases are RAS-activated switches that initiate signalling through the MAP kinase cascade to control cellular proliferation, differentiation and survival. RAF activity is tightly ...RAF family kinases are RAS-activated switches that initiate signalling through the MAP kinase cascade to control cellular proliferation, differentiation and survival. RAF activity is tightly regulated and inappropriate activation is a frequent cause of cancer; however, the structural basis for RAF regulation is poorly understood at present. Here we use cryo-electron microscopy to determine autoinhibited and active-state structures of full-length BRAF in complexes with MEK1 and a 14-3-3 dimer. The reconstruction reveals an inactive BRAF-MEK1 complex restrained in a cradle formed by the 14-3-3 dimer, which binds the phosphorylated S365 and S729 sites that flank the BRAF kinase domain. The BRAF cysteine-rich domain occupies a central position that stabilizes this assembly, but the adjacent RAS-binding domain is poorly ordered and peripheral. The 14-3-3 cradle maintains autoinhibition by sequestering the membrane-binding cysteine-rich domain and blocking dimerization of the BRAF kinase domain. In the active state, these inhibitory interactions are released and a single 14-3-3 dimer rearranges to bridge the C-terminal pS729 binding sites of two BRAFs, which drives the formation of an active, back-to-back BRAF dimer. Our structural snapshots provide a foundation for understanding normal RAF regulation and its mutational disruption in cancer and developmental syndromes. | |||||||||
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_20552.map.gz | 5.2 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-20552-v30.xml emd-20552.xml | 14 KB 14 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_20552.png | 60.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20552 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20552 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_20552_validation.pdf.gz | 310.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_20552_full_validation.pdf.gz | 310.3 KB | 表示 | |
XML形式データ | emd_20552_validation.xml.gz | 6.1 KB | 表示 | |
CIF形式データ | emd_20552_validation.cif.gz | 6.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20552 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20552 | 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_20552.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Structure of a MAPK pathway complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.11 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
-試料の構成要素
-全体 : ERK pathway complex
全体 | 名称: ERK pathway complex |
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要素 |
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-超分子 #1: ERK pathway complex
超分子 | 名称: ERK pathway complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 280 kDa/nm |
-分子 #1: Serine/threonine-protein kinase B-raf
分子 | 名称: Serine/threonine-protein kinase B-raf / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO / EC番号: non-specific serine/threonine protein kinase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 89.306812 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MSYYHHHHHH HHDIPTTENL YFQGAMDMAA LSGGGGGGAE PGQALFNGDM EPEAGAGAGA AASSAADPAI PEEVWNIKQM IKLTQEHIE ALLDKFGGEH NPPSIYLEAY EEYTSKLDAL QQREQQLLES LGNGTDFSVS SSASMDTVTS SSSSSLSVLP S SLSVFQNP ...文字列: MSYYHHHHHH HHDIPTTENL YFQGAMDMAA LSGGGGGGAE PGQALFNGDM EPEAGAGAGA AASSAADPAI PEEVWNIKQM IKLTQEHIE ALLDKFGGEH NPPSIYLEAY EEYTSKLDAL QQREQQLLES LGNGTDFSVS SSASMDTVTS SSSSSLSVLP S SLSVFQNP TDVARSNPKS PQKPIVRVFL PNKQRTVVPA RCGVTVRDSL KKALMMRGLI PECCAVYRIQ DGEKKPIGWD TD ISWLTGE ELHVEVLENV PLTTHNFVRK TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSK FFEHHP IPQEEASLAE TALTSGSSPS APASDSIGPQ ILTSPSPSKS IPIPQPFRPA DEDHRNQFGQ RDRSSAAPNV HINT IEPVN IDDLIRDQGF RGDGGSTTGL SATPPASLPG SLTNVKALQK SPGPQRERKS SSSSEDRNRM KTLGRRDSSD DWEIP DGQI TVGQRIGSGS FGTVYKGKWH GDVAVKMLNV TAPTPQQLQA FKNEVGVLRK TRHVNILLFM GYSTKPQLAI VTQWCE GSS LYHHLHIIET KFEMIKLIDI ARQTAQGMDY LHAKSIIHRD LKSNNIFLHE DLTVKIGDFG LATVKSRWSG SHQFEQL SG SILWMAPEVI RMQDKNPYSF QSDVYAFGIV LYELMTGQLP YSNINNRDQI IFMVGRGYLS PDLSKVRSNC PKAMKRLM A ECLKKKRDER PLFPQILASI ELLARSLPKI HRSA(SEP)EPSLN RAGFQTEDFS LYACASPKTP IQAGGYGAFP VHGTS AWSH PQFEK |
-分子 #2: Dual specificity mitogen-activated protein kinase kinase 1
分子 | 名称: Dual specificity mitogen-activated protein kinase kinase 1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO / EC番号: mitogen-activated protein kinase kinase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 45.835414 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGSSHHHHHH SAVDENLYFQ GGMPKKKPTP IQLNPAPDGS AVNGTSSAET NLEALQKKLE ELELDEQQRK RLEAFLTQKQ KVGELKDDD FEKISELGAG NGGVVFKVSH KPSGLVMARK LIHLEIKPAI RNQIIRELQV LHECNSPYIV GFYGAFYSDG E ISICMEHM ...文字列: MGSSHHHHHH SAVDENLYFQ GGMPKKKPTP IQLNPAPDGS AVNGTSSAET NLEALQKKLE ELELDEQQRK RLEAFLTQKQ KVGELKDDD FEKISELGAG NGGVVFKVSH KPSGLVMARK LIHLEIKPAI RNQIIRELQV LHECNSPYIV GFYGAFYSDG E ISICMEHM DGGSLDQVLK KAGRIPEQIL GKVSIAVIKG LTYLREKHKI MHRDVKPSNI LVNSRGEIKL CDFGVSGQLI DA MANAFVG TRSYMSPERL QGTHYSVQSD IWSMGLSLVE MAVGRYPIPP PDAKELELMF GCQVEGDAAE TPPRPRTPGR PLS SYGMDS RPPMAIFELL DYIVNEPPPK LPSGVFSLEF QDFVNKCLIK NPAERADLKQ LMVHAFIKRS DAEEVDFAGW LCST IGLNQ PSTPTHAAG |
-分子 #3: 14-3-3 protein zeta
分子 | 名称: 14-3-3 protein zeta / タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Beet armyworm (シロイチモジヨトウ) |
分子量 | 理論値: 28.108514 KDa |
配列 | 文字列: MSVDKEELVQ RAKLAEQAER YDDMAAAMKE VTETGVELSN EERNLLSVAY KNVVGARRSS WRVISSIEQK TEGSERKQQM AKEYRVKVE KELREICYDV LGLLDKHLIP KASNPESKVF YLKMKGDYYR YLAEVATGET RNSVVEDSQK AYQDAFEISK A KMQPTHPI ...文字列: MSVDKEELVQ RAKLAEQAER YDDMAAAMKE VTETGVELSN EERNLLSVAY KNVVGARRSS WRVISSIEQK TEGSERKQQM AKEYRVKVE KELREICYDV LGLLDKHLIP KASNPESKVF YLKMKGDYYR YLAEVATGET RNSVVEDSQK AYQDAFEISK A KMQPTHPI RLGLALNFSV FYYEILNSPD KACQLAKQAF DDAIAELDTL NEDSYKDSTL IMQLLRDNLT LWTSDTQGDG DE PAEGGDN |
-分子 #4: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 4 / コピー数: 1 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-分子 #5: 5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)imidazo[1,5-a...
分子 | 名称: 5-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide タイプ: ligand / ID: 5 / コピー数: 1 / 式: LCJ |
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分子量 | 理論値: 456.21 Da |
Chemical component information | ChemComp-LCJ: |
-分子 #6: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER
分子 | 名称: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / タイプ: ligand / ID: 6 / コピー数: 1 / 式: AGS |
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分子量 | 理論値: 523.247 Da |
Chemical component information | ChemComp-AGS: |
-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
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 53.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: OTHER / 撮影モード: OTHER |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 5.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 595672 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
-原子モデル構築 1
精密化 | プロトコル: RIGID BODY FIT |
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得られたモデル | PDB-6q0t: |