+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-23919 | |||||||||
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タイトル | Cryo-EM structure of 2:2 c-MET/HGF holo-complex | |||||||||
マップデータ | Cryo-EM map of 2:2 c-MET/HGF holo-complex. | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 regulation of p38MAPK cascade / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / skeletal muscle cell proliferation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins ...regulation of p38MAPK cascade / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / skeletal muscle cell proliferation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / hepatocyte growth factor receptor signaling pathway / semaphorin receptor activity / positive regulation of endothelial cell chemotaxis / MET receptor recycling / 膵臓 / MET activates PTPN11 / MET activates RAP1 and RAC1 / Sema4D mediated inhibition of cell attachment and migration / myoblast proliferation / MET activates PI3K/AKT signaling / negative regulation of stress fiber assembly / negative regulation of Rho protein signal transduction / MET activates PTK2 signaling / positive regulation of DNA biosynthetic process / cellular response to hepatocyte growth factor stimulus / branching morphogenesis of an epithelial tube / positive chemotaxis / negative regulation of thrombin-activated receptor signaling pathway / negative regulation of release of cytochrome c from mitochondria / chemoattractant activity / negative regulation of interleukin-6 production / semaphorin-plexin signaling pathway / positive regulation of interleukin-10 production / 上皮間葉転換 / establishment of skin barrier / positive regulation of osteoblast differentiation / MET activates RAS signaling / negative regulation of peptidyl-serine phosphorylation / 食作用 / MECP2 regulates neuronal receptors and channels / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / positive regulation of microtubule polymerization / Interleukin-7 signaling / cell chemotaxis / basal plasma membrane / negative regulation of autophagy / InlB-mediated entry of Listeria monocytogenes into host cell / platelet alpha granule lumen / liver development / epithelial cell proliferation / molecular function activator activity / growth factor activity / cell morphogenesis / Negative regulation of MET activity / 受容体型チロシンキナーゼ / neuron differentiation / negative regulation of inflammatory response / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / positive regulation of peptidyl-tyrosine phosphorylation / 遊走 / Platelet degranulation / PIP3 activates AKT signaling / mitotic cell cycle / nervous system development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / positive regulation of MAPK cascade / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / positive regulation of cell migration / positive regulation of protein phosphorylation / リン酸化 / signaling receptor binding / negative regulation of apoptotic process / 細胞膜 / シグナル伝達 / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / ATP binding / 生体膜 / identical protein binding / 細胞膜 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: 4.8 Å | |||||||||
データ登録者 | Uchikawa E / Chen ZM / Xiao GY / Zhang XW / Bai XC | |||||||||
引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Structural basis of the activation of c-MET receptor. 著者: Emiko Uchikawa / Zhiming Chen / Guan-Yu Xiao / Xuewu Zhang / Xiao-Chen Bai / 要旨: The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic ...The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic progression of cancer cells. C-MET can be activated by either hepatocyte growth factor (HGF), or its natural isoform NK1. Here, we report the cryo-EM structures of c-MET/HGF and c-MET/NK1 complexes in the active state. The c-MET/HGF complex structure reveals that, by utilizing two distinct interfaces, one HGF molecule is sufficient to induce a specific dimerization mode of c-MET for receptor activation. The binding of heparin as well as a second HGF to the 2:1 c-MET:HGF complex further stabilize this active conformation. Distinct to HGF, NK1 forms a stable dimer, and bridges two c-METs in a symmetrical manner for activation. Collectively, our studies provide structural insights into the activation mechanisms of c-MET, and reveal how two isoforms of the same ligand use dramatically different mechanisms to activate the receptor. | |||||||||
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_23919.map.gz | 70.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-23919-v30.xml emd-23919.xml | 13.3 KB 13.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_23919.png | 181.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-23919 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23919 | 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_23919.map.gz / 形式: CCP4 / 大きさ: 75.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Cryo-EM map of 2:2 c-MET/HGF holo-complex. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.08 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 : 2:2 c-MET/HGF holo-complex
全体 | 名称: 2:2 c-MET/HGF holo-complex |
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要素 |
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-超分子 #1: 2:2 c-MET/HGF holo-complex
超分子 | 名称: 2:2 c-MET/HGF holo-complex / 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) |
組換発現 | 生物種: Homo sapiens (ヒト) |
-分子 #1: Hepatocyte growth factor
分子 | 名称: Hepatocyte growth factor / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 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: 83.249828 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK TKKVNTADQC ANRCTRNKGL PFTCKAFVF DKARKQCLWF PFNSMSSGVK KEFGHEFDLY ENKDYIRNCI IGKGRSYKGT VSITKSGIKC QPWSSMIPHE H SFLPSSYR ...文字列: MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK TKKVNTADQC ANRCTRNKGL PFTCKAFVF DKARKQCLWF PFNSMSSGVK KEFGHEFDLY ENKDYIRNCI IGKGRSYKGT VSITKSGIKC QPWSSMIPHE H SFLPSSYR GKDLQENYCR NPRGEEGGPW CFTSNPEVRY EVCDIPQCSE VECMTCNGES YRGLMDHTES GKICQRWDHQ TP HRHKFLP ERYPDKGFDD NYCRNPDGQP RPWCYTLDPH TRWEYCAIKT CADNTMNDTD VPLETTECIQ GQGEGYRGTV NTI WNGIPC QRWDSQYPHE HDMTPENFKC KDLRENYCRN PDGSESPWCF TTDPNIRVGY CSQIPNCDMS HGQDCYRGNG KNYM GNLSQ TRSGLTCSMW DKNMEDLHRH IFWEPDASKL NENYCRNPDD DAHGPWCYTG NPLIPWDYCP ISRCEGDTTP TIVNL DHPV ISCAKTKQLR VVNGIPTRTN IGWMVSLRYR NKHICGGSLI KESWVLTARQ CFPSRDLKDY EAWLGIHDVH GRGDEK CKQ VLNVSQLVYG PEGSDLVLMK LARPAVLDDF VSTIDLPNYG CTIPEKTSCS VYGWGYTGLI NYDGLLRVAH LYIMGNE KC SQHHRGKVTL NESEICAGAE KIGSGPCEGD YGGPLVCEQH KMRMVLGVIV PGRGCAIPNR PGIFVRVAYY AKWIHKII L TYKVPQS |
-分子 #2: Hepatocyte growth factor receptor
分子 | 名称: Hepatocyte growth factor receptor / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO / EC番号: 受容体型チロシンキナーゼ |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 155.720625 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH HIFLGATNYI YVLNEEDLQK VAEYKTGPV LEHPDCFPCQ DCSSKANLSG GVWKDNINMA LVVDTYYDDQ LISCGSVNRG TCQRHVFPHN HTADIQSEVH C IFSPQIEE ...文字列: MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH HIFLGATNYI YVLNEEDLQK VAEYKTGPV LEHPDCFPCQ DCSSKANLSG GVWKDNINMA LVVDTYYDDQ LISCGSVNRG TCQRHVFPHN HTADIQSEVH C IFSPQIEE PSQCPDCVVS ALGAKVLSSV KDRFINFFVG NTINSSYFPD HPLHSISVRR LKETKDGFMF LTDQSYIDVL PE FRDSYPI KYVHAFESNN FIYFLTVQRE TLDAQTFHTR IIRFCSINSG LHSYMEMPLE CILTEKRKKR STKKEVFNIL QAA YVSKPG AQLARQIGAS LNDDILFGVF AQSKPDSAEP MDRSAMCAFP IKYVNDFFNK IVNKNNVRCL QHFYGPNHEH CFNR TLLRN SSGCEARRDE YRTEFTTALQ RVDLFMGQFS EVLLTSISTF IKGDLTIANL GTSEGRFMQV VVSRSGPSTP HVNFL LDSH PVSPEVIVEH TLNQNGYTLV ITGKKITKIP LNGLGCRHFQ SCSQCLSAPP FVQCGWCHDK CVRSEECLSG TWTQQI CLP AIYKVFPNSA PLEGGTRLTI CGWDFGFRRN NKFDLKKTRV LLGNESCTLT LSESTMNTLK CTVGPAMNKH FNMSIII SN GHGTTQYSTF SYVDPVITSI SPKYGPMAGG TLLTLTGNYL NSGNSRHISI GGKTCTLKSV SNSILECYTP AQTISTEF A VKLKIDLANR ETSIFSYRED PIVYEIHPTK SFISGGSTIT GVGKNLNSVS VPRMVINVHE AGRNFTVACQ HRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV FKPFEKPVMI SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHS EAVLCTVPND LLKLNSELNI EWKQAISSTV LGKVIVQPDQ NFTGLIAGVV SISTALLLLL GFFLWLKKRK Q IKDLGSEL VRYDARVHTP HLDRLVSARS VSPTTEMVSN ESVDYRATFP EDQFPNSSQN GSCRQVQYPL TDMSPILTSG DS DISSPLL QNTVHIDLSA LNPELVQAVQ HVVIGPSSLI VHFNEVIGRG HFGCVYHGTL LDNDGKKIHC AVKSLNRITD IGE VSQFLT EGIIMKDFSH PNVLSLLGIC LRSEGSPLVV LPYMKHGDLR NFIRNETHNP TVKDLIGFGL QVAKGMKYLA SKKF VHRDL AARNCMLDEK FTVKVADFGL ARDMYDKEYY SVHNKTGAKL PVKWMALESL QTQKFTTKSD VWSFGVLLWE LMTRG APPY PDVNTFDITV YLLQGRRLLQ PEYCPDPLYE VMLKCWHPKA EMRPSFSELV SRISAIFSTF IGEHYVHVNA TYVNVK CVA PYPSLLSSED NADDEVDTRP ASFWETS |
-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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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE |
-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 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy |
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 BIOQUANTUM (6k x 4k) 平均電子線量: 60.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: RELION |
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最終 3次元分類 | ソフトウェア - 名称: RELION |
最終 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: RELION |
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: 4.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION / 使用した粒子像数: 25787 |