+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-27330 | ||||||||||||||||||||||||||||||||||||||||||||||||
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タイトル | PI 3-kinase alpha with nanobody 3-159 | ||||||||||||||||||||||||||||||||||||||||||||||||
マップデータ | Human PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-159 bound, Full map | ||||||||||||||||||||||||||||||||||||||||||||||||
試料 |
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キーワード | Phosphoinositide 3-kinase (PI3K) / activation / inhibition / nanobody / conformational changes / STRUCTURAL PROTEIN / TRANSFERASE | ||||||||||||||||||||||||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / response to butyrate / phosphatidylinositol 3-kinase regulator activity / IRS-mediated signalling ...perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / response to butyrate / phosphatidylinositol 3-kinase regulator activity / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / positive regulation of focal adhesion disassembly / phosphatidylinositol 3-kinase activator activity / interleukin-18-mediated signaling pathway / PI3K events in ERBB4 signaling / myeloid leukocyte migration / 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase regulatory subunit binding / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / positive regulation of protein localization to membrane / Activated NTRK3 signals through PI3K / cis-Golgi network / ErbB-3 class receptor binding / negative regulation of fibroblast apoptotic process / kinase activator activity / phosphatidylinositol 3-kinase complex, class IB / vasculature development / transmembrane receptor protein tyrosine kinase adaptor activity / RHOF GTPase cycle / RHOD GTPase cycle / Signaling by cytosolic FGFR1 fusion mutants / regulation of cellular respiration / positive regulation of endoplasmic reticulum unfolded protein response / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IA / enzyme-substrate adaptor activity / anoikis / phosphatidylinositol 3-kinase complex / Nephrin family interactions / Signaling by LTK in cancer / PI3K events in ERBB2 signaling / RND1 GTPase cycle / relaxation of cardiac muscle / Costimulation by the CD28 family / Signaling by LTK / positive regulation of leukocyte migration / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / MET activates PI3K/AKT signaling / RND2 GTPase cycle / PI3K/AKT activation / positive regulation of filopodium assembly / RND3 GTPase cycle / phosphatidylinositol-4,5-bisphosphate 3-kinase / vascular endothelial growth factor signaling pathway / negative regulation of stress fiber assembly / growth hormone receptor signaling pathway / phosphatidylinositol 3-kinase / natural killer cell mediated cytotoxicity / insulin binding / phosphatidylinositol-3-phosphate biosynthetic process / RHOV GTPase cycle / negative regulation of macroautophagy / 1-phosphatidylinositol-3-kinase activity / Signaling by ALK / negative regulation of cell-matrix adhesion / RHOB GTPase cycle / GP1b-IX-V activation signalling / GAB1 signalosome / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / PI-3K cascade:FGFR2 / protein kinase activator activity / response to dexamethasone / PI-3K cascade:FGFR4 / RHOC GTPase cycle / RHOJ GTPase cycle / PI-3K cascade:FGFR1 / negative regulation of osteoclast differentiation / intracellular glucose homeostasis / CD28 dependent PI3K/Akt signaling / Synthesis of PIPs at the plasma membrane / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / CDC42 GTPase cycle / RHOU GTPase cycle / negative regulation of anoikis / intercalated disc / RET signaling / T cell differentiation / Interleukin-3, Interleukin-5 and GM-CSF signaling / insulin receptor substrate binding / RHOG GTPase cycle / extrinsic apoptotic signaling pathway via death domain receptors / regulation of multicellular organism growth / PI3K Cascade / RHOA GTPase cycle / endothelial cell migration 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: 2.8 Å | ||||||||||||||||||||||||||||||||||||||||||||||||
データ登録者 | Hart JR / Liu X / Pan C / Liang A / Ueno L / Xu Y / Quezada A / Zou X / Yang S / Zhou Q ...Hart JR / Liu X / Pan C / Liang A / Ueno L / Xu Y / Quezada A / Zou X / Yang S / Zhou Q / Schoonooghe S / Hassanzadeh-Ghassabeh G / Xia T / Shui W / Yang D / Vogt PK / Wang M-W | ||||||||||||||||||||||||||||||||||||||||||||||||
資金援助 | 米国, 中国, 15件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2022 タイトル: Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα. 著者: Jonathan R Hart / Xiao Liu / Chen Pan / Anyi Liang / Lynn Ueno / Yingna Xu / Alexandra Quezada / Xinyu Zou / Su Yang / Qingtong Zhou / Steve Schoonooghe / Gholamreza Hassanzadeh-Ghassabeh / ...著者: Jonathan R Hart / Xiao Liu / Chen Pan / Anyi Liang / Lynn Ueno / Yingna Xu / Alexandra Quezada / Xinyu Zou / Su Yang / Qingtong Zhou / Steve Schoonooghe / Gholamreza Hassanzadeh-Ghassabeh / Tian Xia / Wenqing Shui / Dehua Yang / Peter K Vogt / Ming-Wei Wang / 要旨: Nanobodies and chemical cross-linking were used to gain information on the identity and positions of flexible domains of PI3Kα. The application of chemical cross-linking mass spectrometry (CXMS) ...Nanobodies and chemical cross-linking were used to gain information on the identity and positions of flexible domains of PI3Kα. The application of chemical cross-linking mass spectrometry (CXMS) facilitated the identification of the p85 domains BH, cSH2, and SH3 as well as their docking positions on the PI3Kα catalytic core. Binding of individual nanobodies to PI3Kα induced activation or inhibition of enzyme activity and caused conformational changes that could be correlated with enzyme function. Binding of nanobody Nb3-126 to the BH domain of p85α substantially improved resolution for parts of the PI3Kα complex, and binding of nanobody Nb3-159 induced a conformation of PI3Kα that is distinct from known PI3Kα structures. The analysis of CXMS data also provided mechanistic insights into the molecular underpinning of the flexibility of PI3Kα. | ||||||||||||||||||||||||||||||||||||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_27330.map.gz | 59.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-27330-v30.xml emd-27330.xml | 21.6 KB 21.6 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_27330_fsc.xml | 11.6 KB | 表示 | FSCデータファイル |
画像 | emd_27330.png | 35.3 KB | ||
マスクデータ | emd_27330_msk_1.map | 64 MB | マスクマップ | |
Filedesc metadata | emd-27330.cif.gz | 7.2 KB | ||
その他 | emd_27330_half_map_1.map.gz emd_27330_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-27330 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27330 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_27330_validation.pdf.gz | 888 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_27330_full_validation.pdf.gz | 887.6 KB | 表示 | |
XML形式データ | emd_27330_validation.xml.gz | 16.5 KB | 表示 | |
CIF形式データ | emd_27330_validation.cif.gz | 21.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27330 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27330 | 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_27330.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 | Human PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-159 bound, Full map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.832 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_27330_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Human PI 3-kinase alpha complex composed of p110alpha...
ファイル | emd_27330_half_map_1.map | ||||||||||||
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注釈 | Human PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-159 bound, Half map A | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Human PI 3-kinase alpha complex composed of p110alpha...
ファイル | emd_27330_half_map_2.map | ||||||||||||
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注釈 | Human PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-159 bound, Half map B | ||||||||||||
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 : Human PI 3-kinase alpha complex composed of p110alpha and p85alph...
全体 | 名称: Human PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-159 bound |
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要素 |
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-超分子 #1: Human PI 3-kinase alpha complex composed of p110alpha and p85alph...
超分子 | 名称: Human PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-159 bound 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: Homo sapiens (ヒト) |
-分子 #1: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit ...
分子 | 名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: phosphatidylinositol-4,5-bisphosphate 3-kinase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 127.822578 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MSYYHHHHHH DYDIPTTENL YFQGAMGSMP PRPSSGELWG IHLMPPRILV ECLLPNGMIV TLECLREATL ITIKHELFKE ARKYPLHQL LQDESSYIFV SVTQEAEREE FFDETRRLCD LRLFQPFLKV IEPVGNREEK ILNREIGFAI GMPVCEFDMV K DPEVQDFR ...文字列: MSYYHHHHHH DYDIPTTENL YFQGAMGSMP PRPSSGELWG IHLMPPRILV ECLLPNGMIV TLECLREATL ITIKHELFKE ARKYPLHQL LQDESSYIFV SVTQEAEREE FFDETRRLCD LRLFQPFLKV IEPVGNREEK ILNREIGFAI GMPVCEFDMV K DPEVQDFR RNILNVCKEA VDLRDLNSPH SRAMYVYPPN VESSPELPKH IYNKLDKGQI IVVIWVIVSP NNDKQKYTLK IN HDCVPEQ VIAEAIRKKT RSMLLSSEQL KLCVLEYQGK YILKVCGCDE YFLEKYPLSQ YKYIRSCIML GRMPNLMLMA KES LYSQLP MDCFTMPSYS RRISTATPYM NGETSTKSLW VINSALRIKI LCATYVNVNI RDIDKIYVRT GIYHGGEPLC DNVN TQRVP CSNPRWNEWL NYDIYIPDLP RAARLCLSIC SVKGRKGAKE EHCPLAWGNI NLFDYTDTLV SGKMALNLWP VPHGL EDLL NPIGVTGSNP NKETPCLELE FDWFSSVVKF PDMSVIEEHA NWSVSREAGF SYSHAGLSNR LARDNELREN DKEQLK AIS TRDPLSEITE QEKDFLWSHR HYCVTIPEIL PKLLLSVKWN SRDEVAQMYC LVKDWPPIKP EQAMELLDCN YPDPMVR GF AVRCLEKYLT DDKLSQYLIQ LVQVLKYEQY LDNLLVRFLL KKALTNQRIG HFFFWHLKSE MHNKTVSQRF GLLLESYC R ACGMYLKHLN RQVEAMEKLI NLTDILKQEK KDETQKVQMK FLVEQMRRPD FMDALQGFLS PLNPAHQLGN LRLEECRIM SSAKRPLWLN WENPDIMSEL LFQNNEIIFK NGDDLRQDML TLQIIRIMEN IWQNQGLDLR MLPYGCLSIG DCVGLIEVVR NSHTIMQIQ CKGGLKGALQ FNSHTLHQWL KDKNKGEIYD AAIDLFTRSC AGYCVATFIL GIGDRHNSNI MVKDDGQLFH I DFGHFLDH KKKKFGYKRE RVPFVLTQDF LIVISKGAQE CTKTREFERF QEMCYKAYLA IRQHANLFIN LFSMMLGSGM PE LQSFDDI AYIRKTLALD KTEQEALEYF MKQMNDAHHG GWTTKMDWIF HTIKQHALN UniProtKB: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform |
-分子 #2: Phosphatidylinositol 3-kinase regulatory subunit alpha
分子 | 名称: Phosphatidylinositol 3-kinase regulatory subunit alpha タイプ: protein_or_peptide / ID: 2 / 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: 83.623203 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MAEGYQYRAL YDYKKEREED IDLHLGDILT VNKGSLVALG FSDGQEARPE EIGWLNGYNE TTGERGDFPG TYVEYIGRKK ISPPTPKPR PPRPLPVAPG SSKTEADVEQ QALTLPDLAE QFAPPDIAPP LLIKLVEAIE KKGLECSTLY RTQSSSNLAE L RQLLDCDT ...文字列: MAEGYQYRAL YDYKKEREED IDLHLGDILT VNKGSLVALG FSDGQEARPE EIGWLNGYNE TTGERGDFPG TYVEYIGRKK ISPPTPKPR PPRPLPVAPG SSKTEADVEQ QALTLPDLAE QFAPPDIAPP LLIKLVEAIE KKGLECSTLY RTQSSSNLAE L RQLLDCDT PSVDLEMIDV HVLADAFKRY LLDLPNPVIP AAVYSEMISL APEVQSSEEY IQLLKKLIRS PSIPHQYWLT LQ YLLKHFF KLSQTSSKNL LNARVLSEIF SPMLFRFSAA SSDNTENLIK VIEILISTEW NERQPAPALP PKPPKPTTVA NNG MNNNMS LQDAEWYWGD ISREEVNEKL RDTADGTFLV RDASTKMHGD YTLTLRKGGN NKLIKIFHRD GKYGFSDPLT FSSV VELIN HYRNESLAQY NPKLDVKLLY PVSKYQQDQV VKEDNIEAVG KKLHEYNTQF QEKSREYDRL YEEYTRTSQE IQMKR TAIE AFNETIKIFE EQCQTQERYS KEYIEKFKRE GNEKEIQRIM HNYDKLKSRI SEIIDSRRRL EEDLKKQAAE YREIDK RMN SIKPDLIQLR KTRDQYLMWL TQKGVRQKKL NEWLGNENTE DQYSLVEDDE DLPHHDEKTW NVGSSNRNKA ENLLRGK RD GTFLVRESSK QGCYACSVVV DGEVKHCVIN KTATGYGFAE PYNLYSSLKE LVLHYQHTSL VQHNDSLNVT LAYPVYAQ Q RR UniProtKB: Phosphatidylinositol 3-kinase regulatory subunit alpha |
-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 | 1.0 mg/mL |
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緩衝液 | pH: 7.6 |
凍結 | 凍結剤: ETHANE |
-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 K3 (6k x 4k) / 平均電子線量: 70.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: OTHER |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |