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基本情報
登録情報 | ![]() | ||||||||||||||||||
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タイトル | Structure of Src in complex with beta-arrestin 1 revealing SH3 binding sites | ||||||||||||||||||
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![]() | GPCR signaling / arrestin / Src / SH3 / SIGNALING PROTEIN-IMMUNE SYSTEM complex / SIGNALING PROTEIN | ||||||||||||||||||
機能・相同性 | ![]() V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / TGFBR3 regulates TGF-beta signaling / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / sensory perception of touch / G alpha (s) signalling events / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin ...V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / TGFBR3 regulates TGF-beta signaling / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / sensory perception of touch / G alpha (s) signalling events / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / regulation of inositol trisphosphate biosynthetic process / alpha-1B adrenergic receptor binding / follicle-stimulating hormone signaling pathway / protein phosphorylated amino acid binding / Lysosome Vesicle Biogenesis / angiotensin receptor binding / AP-2 adaptor complex binding / Ub-specific processing proteases / MAP2K and MAPK activation / Golgi Associated Vesicle Biogenesis / hemostasis / Signaling by ERBB2 / Nuclear signaling by ERBB4 / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions / Co-stimulation by CD28 / Co-inhibition by CTLA4 / EPHA-mediated growth cone collapse / Ephrin signaling / G alpha (i) signalling events / GP1b-IX-V activation signalling / Thrombin signalling through proteinase activated receptors (PARs) / VEGFR2 mediated cell proliferation / RET signaling / Receptor Mediated Mitophagy / ADP signalling through P2Y purinoceptor 1 / RAF activation / PIP3 activates AKT signaling / EPH-ephrin mediated repulsion of cells / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Activated NTRK3 signals through PI3K / Downstream signal transduction / Downregulation of ERBB4 signaling / Cyclin D associated events in G1 / Regulation of RUNX3 expression and activity / telencephalon development / MAP2K and MAPK activation / Cargo recognition for clathrin-mediated endocytosis / Integrin signaling / GRB2:SOS provides linkage to MAPK signaling for Integrins / DCC mediated attractive signaling / MET activates PTK2 signaling / Extra-nuclear estrogen signaling / EPHB-mediated forward signaling / clathrin adaptor activity / p130Cas linkage to MAPK signaling for integrins / VEGFA-VEGFR2 Pathway / Clathrin-mediated endocytosis / negative regulation of interleukin-8 production / regulation of G protein-coupled receptor signaling pathway / connexin binding / G protein-coupled receptor internalization / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / arrestin family protein binding / mitogen-activated protein kinase kinase binding / Thrombin signalling through proteinase activated receptors (PARs) / response to morphine / clathrin binding / stress fiber assembly / positive regulation of Rho protein signal transduction / positive regulation of vasoconstriction / pseudopodium / negative regulation of intrinsic apoptotic signaling pathway / positive regulation of systemic arterial blood pressure / negative regulation of interleukin-6 production / positive regulation of intracellular signal transduction / positive regulation of receptor internalization / progesterone receptor signaling pathway / negative regulation of Notch signaling pathway / endocytic vesicle / phototransduction / positive regulation of insulin secretion involved in cellular response to glucose stimulus / activation of adenylate cyclase activity / cellular response to hormone stimulus / immune system process / insulin-like growth factor receptor binding / clathrin-coated pit / positive regulation of protein ubiquitination / response to cytokine / negative regulation of protein ubiquitination / GTPase activator activity / nuclear estrogen receptor binding / negative regulation of extrinsic apoptotic signaling pathway / phosphoprotein binding 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: 3.34 Å | ||||||||||||||||||
![]() | Pakharukova N / Bansia H / Bassford DK / des Georges A / Lefkowitz RJ | ||||||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy. 著者: Natalia Pakharukova / Brittany N Thomas / Harsh Bansia / Linus Li / Rinat R Abzalimov / Jihee Kim / Alem W Kahsai / Biswaranjan Pani / Dana K Bassford / Shibo Liu / Xingdong Zhang / Amedee ...著者: Natalia Pakharukova / Brittany N Thomas / Harsh Bansia / Linus Li / Rinat R Abzalimov / Jihee Kim / Alem W Kahsai / Biswaranjan Pani / Dana K Bassford / Shibo Liu / Xingdong Zhang / Amedee des Georges / Robert J Lefkowitz / ![]() 要旨: Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use ...Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use cryo-electron microscopy to elucidate how βarr1 recruits and activates non-receptor tyrosine kinase Src. βarr1 binds Src SH3 domain via two distinct sites: a polyproline site in the N-domain and a non-proline site in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3 which is critical for Src autoinhibition, suggesting that βarr1 activates Src by SH3 domain displacement. Binding of SH3 to the central crest region induces structural rearrangements in the β-strand V, finger, and middle loops of βarr1 and interferes with βarr1 coupling to the receptor core potentially impacting receptor desensitization and downstream signaling. | ||||||||||||||||||
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 | ![]() | 97.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 26.4 KB 26.4 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.9 KB | 表示 | ![]() |
画像 | ![]() | 160.9 KB | ||
Filedesc metadata | ![]() | 7.6 KB | ||
その他 | ![]() ![]() ![]() | 85.7 MB 95.4 MB 95.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 875.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 874.9 KB | 表示 | |
XML形式データ | ![]() | 18.1 KB | 表示 | |
CIF形式データ | ![]() | 23.4 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 9bt8MC ![]() 9cx3C ![]() 9cx9C ![]() 41882 ![]() 41971 M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.44 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
-追加マップ: Map after sharpening with DeepEM enhancer
ファイル | emd_44881_additional_1.map | ||||||||||||
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注釈 | Map after sharpening with DeepEM enhancer | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_44881_half_map_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: #1
ファイル | emd_44881_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Beta-arrestin 1 bound to a G protein-coupled receptor phosphopept...
全体 | 名称: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopeptide, nanobody 32 and antibody fragment Fab30 in complex with three-domain Src (SH3-SH2-SH1). |
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要素 |
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-超分子 #1: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopept...
超分子 | 名称: Beta-arrestin 1 bound to a G protein-coupled receptor phosphopeptide, nanobody 32 and antibody fragment Fab30 in complex with three-domain Src (SH3-SH2-SH1). 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: Proto-oncogene tyrosine-protein kinase Src
分子 | 名称: Proto-oncogene tyrosine-protein kinase Src / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: non-specific protein-tyrosine kinase |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 54.524465 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGSSHHHHHH DYDIPTTENL YFQGHMVTTF VALYDYESCT ETDLSFKKGE RLQIVNNTEG DWWLAHSLTT GQTGYIPSNY VAPSDSIQA EEWYFGKITR RESERLLLNP ENPRGTFLVR ESETTKGAYS LSVSDFDNAK GLNVKHYKIR KLDSGGFYIT S RTQFSSLQ ...文字列: MGSSHHHHHH DYDIPTTENL YFQGHMVTTF VALYDYESCT ETDLSFKKGE RLQIVNNTEG DWWLAHSLTT GQTGYIPSNY VAPSDSIQA EEWYFGKITR RESERLLLNP ENPRGTFLVR ESETTKGAYS LSVSDFDNAK GLNVKHYKIR KLDSGGFYIT S RTQFSSLQ QLVAYYSKHA DGLSHRLTNV SPTSKPQTQG LAKDAWEIPR ESLRLEVKLG QGSFGEVWMG TWNGTTRVAI KT LKPGTMS PEAFLQEAQV MKKLRHEKLV QLYAVVSEEP IYIVTEYMSK GSLLDFLKGE MGKYLRLPQL VDMAAQIASG MAY VERMNY VHRDLRAANI LVGENLVSKV ADFGLARLIE DNEYTARQGA KFPIKWTAPE AALYGRFTIK SDVWSFGILL TELT TKGRV PYPGMVNREV LDQVERGYRM PCPPECPESL HDLMCQCWRK DPEERPTFEY LQAFLEDYFT STEPQYQPGE NL UniProtKB: Proto-oncogene tyrosine-protein kinase Src |
-分子 #2: Antibody fragment Fab30, heavy chain
分子 | 名称: Antibody fragment Fab30, heavy chain / 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: ![]() |
分子量 | 理論値: 25.512354 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...文字列: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDK THHHHHHHH |
-分子 #3: Vasopressin V2 receptor
分子 | 名称: Vasopressin V2 receptor / タイプ: protein_or_peptide / ID: 3 詳細: Synthetic phosphopeptide mimicking the C-tail of vasopressin 2 receptor 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: 3.550936 KDa |
配列 | 文字列: ARGR(TPO)PP(SEP)LG PQDE(SEP)C(TPO)(TPO)A(SEP) (SEP)(SEP)LAKDTSS UniProtKB: Vasopressin V2 receptor |
-分子 #4: Nanobody 32
分子 | 名称: Nanobody 32 / 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: ![]() ![]() |
分子量 | 理論値: 13.665136 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QVQLQESGGG LVQAGGSLRL SCVVSGFFFD TVTMAWYRRA PGKHRELVAS ATAGGTTTYA DSVKDRFTIS RDNAKNTVYL QMNSLKPED TAVYYCNTFV RSLSWGQGTQ VTVSSHHHHH HEPEA |
-分子 #5: Beta-arrestin-1
分子 | 名称: Beta-arrestin-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: ![]() ![]() |
分子量 | 理論値: 44.08116 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GDKGTRVFKK ASPNGKLTVY LGKRDFVDHI DLVDPVDGVV LVDPEYLKER RVYVTLTVAF RYGREDLDVL GLTFRKDLFV ANVQSFPPA PEDKKPLTRL QERLIKKLGE HAYPFTFEIC PNLPSSVTLQ PGPEDTGKAL GVDYEVKAFV AENLEEKIHK R NSVRLVIR ...文字列: GDKGTRVFKK ASPNGKLTVY LGKRDFVDHI DLVDPVDGVV LVDPEYLKER RVYVTLTVAF RYGREDLDVL GLTFRKDLFV ANVQSFPPA PEDKKPLTRL QERLIKKLGE HAYPFTFEIC PNLPSSVTLQ PGPEDTGKAL GVDYEVKAFV AENLEEKIHK R NSVRLVIR KVQYAPERPG PQPTAETTRQ FLMSDKPLHL EASLDKEIYY HGEPISVNVH VTNNTNKTVK KIKISVRQYA DI VLFNTAQ YKVPVAMEEA DDTVAPSSTF SKVYTLTPFL ANNREKRGLA LDGKLKHEDT NLASSTLLRE GANREILGII VSY KVKVKL VVSRGGLLGD LASSDVAVEL PFTLMHPKPK EEPPHREVPE SETPVDTNLI ELDTNDDDIV FEDFAR UniProtKB: Beta-arrestin-1 |
-分子 #6: Antibody fragment Fab30, light chain
分子 | 名称: Antibody fragment Fab30, light chain / タイプ: protein_or_peptide / ID: 6 / 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: 23.435064 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...文字列: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-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
濃度 | 7 mg/mL |
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緩衝液 | pH: 7.5 |
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 |
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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 K3 (6k x 4k) / 平均電子線量: 55.0 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 / 最大 デフォーカス(公称値): 2.4 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
初期モデル |
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得られたモデル | ![]() PDB-9bt8: |