登録情報 データベース : EMDB / ID : EMD-27334 ダウンロードとリンクタイトル PI 3-kinase alpha with nanobody 3-142 マップデータHuman PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-142 bound, Full map 詳細 試料複合体 : Human PI 3-kinase alpha complex composed of p110alpha and p85alpha with nanobody 3-142 boundタンパク質・ペプチド : Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformタンパク質・ペプチド : Phosphatidylinositol 3-kinase regulatory subunit alphaリガンド : water 詳細 キーワード Phosphoinositide 3-kinase (PI3K) / activation / inhibition / nanobody / conformational changes / STRUCTURAL PROTEIN / TRANSFERASE機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
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 / phosphatidylinositol 3-kinase regulator activity / response to butyrate / positive regulation of focal adhesion disassembly ... 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 / phosphatidylinositol 3-kinase regulator activity / response to butyrate / positive regulation of focal adhesion disassembly / autosome genomic imprinting / IRS-mediated signalling / cellular response to hydrostatic pressure / 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 / cardiac muscle cell contraction / RHOF GTPase cycle / kinase activator activity / phosphatidylinositol 3-kinase complex, class IB / vasculature development / transmembrane receptor protein tyrosine kinase adaptor activity / RHOD GTPase cycle / Signaling by cytosolic FGFR1 fusion mutants / regulation of cellular respiration / positive regulation of endoplasmic reticulum unfolded protein response / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase complex, class IA / anoikis / phosphatidylinositol 3-kinase complex / Nephrin family interactions / RND1 GTPase cycle / Costimulation by the CD28 family / relaxation of cardiac muscle / 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 / RND3 GTPase cycle / positive regulation of filopodium assembly / 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 / insulin binding / phosphatidylinositol-3-phosphate biosynthetic process / RHOV GTPase cycle / 1-phosphatidylinositol-3-kinase activity / negative regulation of cell-matrix adhesion / Signaling by ALK / RHOB GTPase cycle / negative regulation of macroautophagy / GP1b-IX-V activation signalling / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / PI-3K cascade:FGFR2 / response to dexamethasone / RHOJ GTPase cycle / PI-3K cascade:FGFR4 / protein kinase activator activity / RHOC 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 / PI3K events in ERBB2 signaling / negative regulation of anoikis / intercalated disc / T cell differentiation / RET signaling / regulation of multicellular organism growth / insulin receptor substrate binding / RHOG GTPase cycle / Interleukin-3, Interleukin-5 and GM-CSF signaling / extrinsic apoptotic signaling pathway via death domain receptors / PI3K Cascade / RHOA GTPase cycle / positive regulation of TOR signaling / endothelial cell migration / RAC2 GTPase cycle / RAC3 GTPase cycle / Role of phospholipids in phagocytosis 類似検索 - 分子機能 PI3Kalpha, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit alpha, SH3 domain / PIK3R1, inter-SH2 domain / PI3K p85 subunit, C-terminal SH2 domain / PI3K regulatory subunit p85-related , inter-SH2 domain / PI3K p85 subunit, N-terminal SH2 domain / Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Rho GTPase-activating protein domain ... PI3Kalpha, catalytic domain / Phosphatidylinositol 3-kinase regulatory subunit alpha, SH3 domain / PIK3R1, inter-SH2 domain / PI3K p85 subunit, C-terminal SH2 domain / PI3K regulatory subunit p85-related , inter-SH2 domain / PI3K p85 subunit, N-terminal SH2 domain / Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain / PI3-kinase family, p85-binding domain / PI3-kinase family, p85-binding domain / Rho GTPase-activating protein domain / RhoGAP domain / Rho GTPase-activating proteins domain profile. / GTPase-activator protein for Rho-like GTPases / Phosphatidylinositol 3-kinase, adaptor-binding domain / Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain profile. / PI3-kinase family, Ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain / PI3-kinase family, ras-binding domain / Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain profile. / Phosphoinositide 3-kinase C2 / Phosphoinositide 3-kinase, region postulated to contain C2 domain / C2 phosphatidylinositol 3-kinase-type domain / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Rho GTPase activation protein / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase / PIK helical domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / C2 domain superfamily / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Armadillo-type fold / Ubiquitin-like domain superfamily / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Phosphatidylinositol 3-kinase regulatory subunit alpha / Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 類似検索 - 構成要素生物種 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 : 3.1 Å 詳細 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 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Cancer Institute (NIH/NCI) R35 CA197582 米国 National Institutes of Health/National Cancer Institute (NIH/NCI) R50 CA243899 米国 National Natural Science Foundation of China (NSFC) 81872915 中国 National Natural Science Foundation of China (NSFC) 82073904 中国 National Natural Science Foundation of China (NSFC) 82121005 中国 National Natural Science Foundation of China (NSFC) 81973373 中国 National Natural Science Foundation of China (NSFC) 31971362 中国 National Natural Science Foundation of China (NSFC) 32171439 中国 National Natural Science Foundation of China (NSFC) 21704064 中国 Other government 2018ZX09735 001 Other government 2018ZX09711002 002 005 Other government 2021ZD0203400 Other government 2018YFA0507000 Other private NNCAS 2017 1 CC Other private ZDKJ2021028
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 登録 2022年6月17日 - ヘッダ(付随情報) 公開 2022年9月21日 - マップ公開 2022年9月21日 - 更新 2024年6月12日 - 現状 2024年6月12日 処理サイト : RCSB / 状態 : 公開
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