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基本情報
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タイトル | Structure of the human CDK8 kinase module | |||||||||
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![]() | Transcription / Mediator / CDK8 / MED12 / MED13 / CKM. | |||||||||
機能・相同性 | ![]() axis elongation involved in somitogenesis / CKM complex / embryonic neurocranium morphogenesis / G0 to G1 transition / oligodendrocyte development / post-anal tail morphogenesis / endoderm development / embryonic brain development / mediator complex / RNA polymerase II CTD heptapeptide repeat Y1 kinase activity ...axis elongation involved in somitogenesis / CKM complex / embryonic neurocranium morphogenesis / G0 to G1 transition / oligodendrocyte development / post-anal tail morphogenesis / endoderm development / embryonic brain development / mediator complex / RNA polymerase II CTD heptapeptide repeat Y1 kinase activity / RNA polymerase II CTD heptapeptide repeat S2 kinase activity / RNA polymerase II CTD heptapeptide repeat T4 kinase activity / RNA polymerase II CTD heptapeptide repeat S5 kinase activity / RNA polymerase II CTD heptapeptide repeat S7 kinase activity / Generic Transcription Pathway / triglyceride homeostasis / nuclear vitamin D receptor binding / [RNA-polymerase]-subunit kinase / nuclear thyroid hormone receptor binding / Wnt signaling pathway, planar cell polarity pathway / cyclin-dependent protein serine/threonine kinase regulator activity / spinal cord development / RSV-host interactions / somatic stem cell population maintenance / negative regulation of Notch signaling pathway / positive regulation of transcription initiation by RNA polymerase II / ubiquitin ligase complex / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / Schwann cell development / cyclin-dependent protein kinase holoenzyme complex / cholesterol homeostasis / transcription coregulator activity / neural tube closure / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / PPARA activates gene expression / beta-catenin binding / Transcriptional regulation of white adipocyte differentiation / NOTCH1 Intracellular Domain Regulates Transcription / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / ubiquitin protein ligase activity / heart development / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / transcription coactivator activity / protein kinase activity / protein ubiquitination / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein serine kinase activity / protein serine/threonine kinase activity / chromatin binding / positive regulation of DNA-templated transcription / nucleolus / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / ATP binding / identical protein binding / nucleus / membrane 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: 3.8 Å | |||||||||
![]() | Chen SF / Chao TC / Kim HJ / Tang HC / Khadka S / Li T / Murakami K / Boyer TG / Tsai KL | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module. 著者: Ti-Chun Chao / Shin-Fu Chen / Hee Jong Kim / Hui-Chi Tang / Hsiang-Ching Tseng / An Xu / Leon Palao / Subash Khadka / Tao Li / Mo-Fan Huang / Dung-Fang Lee / Kenji Murakami / Thomas G Boyer / Kuang-Lei Tsai / ![]() 要旨: The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex ...The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function. | |||||||||
履歴 |
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構造の表示
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-EMDBアーカイブ
マップデータ | ![]() | 156 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 25.4 KB 25.4 KB | 表示 表示 | ![]() |
画像 | ![]() | 76.2 KB | ||
Filedesc metadata | ![]() | 9.5 KB | ||
その他 | ![]() ![]() | 131.5 MB 131.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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
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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: 1.0701 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
-ハーフマップ: #2
ファイル | emd_41502_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_41502_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 : human CDK8 kinase module
全体 | 名称: human CDK8 kinase module |
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要素 |
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-超分子 #1: human CDK8 kinase module
超分子 | 名称: human CDK8 kinase module / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Mediator of RNA polymerase II transcription subunit 12
分子 | 名称: Mediator of RNA polymerase II transcription subunit 12 タイプ: protein_or_peptide / ID: 1 / 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: 243.354891 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MAAFGILSYE HRPLKRPRLG PPDVYPQDPK QKEDELTALN VKQGFNNQPA VSGDEHGSAK NVSFNPAKIS SNFSSIIAEK LRCNTLPDT GRRKPQVNQK DNFWLVTARS QSAINTWFTD LAGTKPLTQL AKKVPIFSKK EEVFGYLAKY TVPVMRAAWL I KMTCAYYA ...文字列: MAAFGILSYE HRPLKRPRLG PPDVYPQDPK QKEDELTALN VKQGFNNQPA VSGDEHGSAK NVSFNPAKIS SNFSSIIAEK LRCNTLPDT GRRKPQVNQK DNFWLVTARS QSAINTWFTD LAGTKPLTQL AKKVPIFSKK EEVFGYLAKY TVPVMRAAWL I KMTCAYYA AISETKVKKR HVDPFMEWTQ IITKYLWEQL QKMAEYYRPG PAGSGGCGST IGPLPHDVEV AIRQWDYTEK LA MFMFQDG MLDRHEFLTW VLECFEKIRP GEDELLKLLL PLLLRYSGEF VQSAYLSRRL AYFCTRRLAL QLDGVSSHSS HVI SAQSTS TLPTTPAPQP PTSSTPSTPF SDLLMCPQHR PLVFGLSCIL QTILLCCPSA LVWHYSLTDS RIKTGSPLDH LPIA PSNLP MPEGNSAFTQ QVRAKLREIE QQIKERGQAV EVRWSFDKCQ EATAGFTIGR VLHTLEVLDS HSFERSDFSN SLDSL CNRI FGLGPSKDGH EISSDDDAVV SLLCEWAVSC KRSGRHRAMV VAKLLEKRQA EIEAERCGES EAADEKGSIA SGSLSA PSA PIFQDVLLQF LDTQAPMLTD PRSESERVEF FNLVLLFCEL IRHDVFSHNM YTCTLISRGD LAFGAPGPRP PSPFDDP AD DPEHKEAEGS SSSKLEDPGL SESMDIDPSS SVLFEDMEKP DFSLFSPTMP CEGKGSPSPE KPDVEKEVKP PPKEKIEG T LGVLYDQPRH VQYATHFPIP QEESCSHECN QRLVVLFGVG KQRDDARHAI KKITKDILKV LNRKGTAETD QLAPIVPLN PGDLTFLGGE DGQKRRRNRP EAFPTAEDIF AKFQHLSHYD QHQVTAQVSR NVLEQITSFA LGMSYHLPLV QHVQFIFDLM EYSLSISGL IDFAIQLLNE LSVVEAELLL KSSDLVGSYT TSLCLCIVAV LRHYHACLIL NQDQMAQVFE GLCGVVKHGM N RSDGSSAE RCILAYLYDL YTSCSHLKNK FGELFSDFCS KVKNTIYCNV EPSESNMRWA PEFMIDTLEN PAAHTFTYTG LG KSLSENP ANRYSFVCNA LMHVCVGHHD PDRVNDIAIL CAELTGYCKS LSAEWLGVLK ALCCSSNNGT CGFNDLLCNV DVS DLSFHD SLATFVAILI ARQCLLLEDL IRCAAIPSLL NAACSEQDSE PGARLTCRIL LHLFKTPQLN PCQSDGNKPT VGIR SSCDR HLLAASQNRI VDGAVFAVLK AVFVLGDAEL KGSGFTVTGG TEELPEEEGG GGSGGRRQGG RNISVETASL DVYAK YVLR SICQQEWVGE RCLKSLCEDS NDLQDPVLSS AQAQRLMQLI CYPHRLLDNE DGENPQRQRI KRILQNLDQW TMRQSS LEL QLMIKQTPNN EMNSLLENIA KATIEVFQQS AETGSSSGST ASNMPSSSKT KPVLSSLERS GVWLVAPLIA KLPTSVQ GH VLKAAGEELE KGQHLGSSSR KERDRQKQKS MSLLSQQPFL SLVLTCLKGQ DEQREGLLTS LYSQVHQIVN NWRDDQYL D DCKPKQLMHE ALKLRLNLVG GMFDTVQRST QQTTEWAMLL LEIIISGTVD MQSNNELFTT VLDMLSVLIN GTLAADMSS ISQGSMEENK RAYMNLAKKL QKELGERQSD SLEKVRQLLP LPKQTRDVIT CEPQGSLIDT KGNKIAGFDS IFKKEGLQVS TKQKISPWD LFEGLKPSAP LSWGWFGTVR VDRRVARGEE QQRLLLYHTH LRPRPRAYYL EPLPLPPEDE EPPAPTLLEP E KKAPEPPK TDKPGAAPPS TEERKKKSTK GKKRSQPATK TEDYGMGPGR SGPYGVTVPP DLLHHPNPGS ITHLNYRQGS IG LYTQNQP LPAGGPRVDP YRPVRLPMQK LPTRPTYPGV LPTTMTGVMG LEPSSYKTSV YRQQQPAVPQ GQRLRQQLQQ SQG MLGQSS VHQMTPSSSY GLQTSQGYTP YVSHVGLQQH TGPAGTMVPP SYSSQPYQST HPSTNPTLVD PTRHLQQRPS GYVH QQAPT YGHGLTSTQR FSHQTLQQTP MISTMTPMSA QGVQAGVRST AILPEQQQQQ QQQQQQQQQQ QQQQQQQQQQ QYHIR QQQQ QQILRQQQQQ QQQQQQQQQQ QQQQQQQQQQ QHQQQQQQQA APPQPQPQSQ PQFQRQGLQQ TQQQQQTAAL VRQLQQ QLS NTQPQPSTNI FGRY UniProtKB: Mediator of RNA polymerase II transcription subunit 12 |
-分子 #2: Mediator of RNA polymerase II transcription subunit 13
分子 | 名称: Mediator of RNA polymerase II transcription subunit 13 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: 239.535906 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSASFVPNGA SLEDCHCNLF CLADLTGIKW KKYVWQGPTS APILFPVTEE DPILSSFSRC LKADVLGVWR RDQRPGRREL WIFWWGEDP SFADLIHHDL SEEEDGVWEN GLSYECRTLL FKAVHNLLER CLMNRNFVRI GKWFVKPYEK DEKPINKSEH L SCSFTFFL ...文字列: MSASFVPNGA SLEDCHCNLF CLADLTGIKW KKYVWQGPTS APILFPVTEE DPILSSFSRC LKADVLGVWR RDQRPGRREL WIFWWGEDP SFADLIHHDL SEEEDGVWEN GLSYECRTLL FKAVHNLLER CLMNRNFVRI GKWFVKPYEK DEKPINKSEH L SCSFTFFL HGDSNVCTSV EINQHQPVYL LSEEHITLAQ QSNSPFQVIL CPFGLNGTLT GQAFKMSDSA TKKLIGEWKQ FY PISCCLK EMSEEKQEDM DWEDDSLAAV EVLVAGVRMI YPACFVLVPQ SDIPTPSPVG STHCSSSCLG VHQVPASTRD PAM SSVTLT PPTSPEEVQT VDPQSVQKWV KFSSVSDGFN SDSTSHHGGK IPRKLANHVV DRVWQECNMN RAQNKRKYSA SSGG LCEEA TAAKVASWDF VEATQRTNCS CLRHKNLKSR NAGQQGQAPS LGQQQQILPK HKTNEKQEKS EKPQKRPLTP FHHRV SVSD DVGMDADSAS QRLVISAPDS QVRFSNIRTN DVAKTPQMHG TEMANSPQPP PLSPHPCDVV DEGVTKTPST PQSQHF YQM PTPDPLVPSK PMEDRIDSLS QSFPPQYQEA VEPTVYVGTA VNLEEDEANI AWKYYKFPKK KDVEFLPPQL PSDKFKD DP VGPFGQESVT SVTELMVQCK KPLKVSDELV QQYQIKNQCL SAIASDAEQE PKIDPYAFVE GDEEFLFPDK KDRQNSER E AGKKHKVEDG TSSVTVLSHE EDAMSLFSPS IKQDAPRPTS HARPPSTSLI YDSDLAVSYT DLDNLFNSDE DELTPGSKK SANGSDDKAS CKESKTGNLD PLSCISTADL HKMYPTPPSL EQHIMGFSPM NMNNKEYGSM DTTPGGTVLE GNSSSIGAQF KIEVDEGFC SPKPSEIKDF SYVYKPENCQ ILVGCSMFAP LKTLPSQYLP PIKLPEECIY RQSWTVGKLE LLSSGPSMPF I KEGDGSNM DQEYGTAYTP QTHTSFGMPP SSAPPSNSGA GILPSPSTPR FPTPRTPRTP RTPRGAGGPA SAQGSVKYEN SD LYSPAST PSTCRPLNSV EPATVPSIPE AHSLYVNLIL SESVMNLFKD CNFDSCCICV CNMNIKGADV GVYIPDPTQE AQY RCTCGF SAVMNRKFGN NSGLFLEDEL DIIGRNTDCG KEAEKRFEAL RATSAEHVNG GLKESEKLSD DLILLLQDQC TNLF SPFGA ADQDPFPKSG VISNWVRVEE RDCCNDCYLA LEHGRQFMDN MSGGKVDEAL VKSSCLHPWS KRNDVSMQCS QDILR MLLS LQPVLQDAIQ KKRTVRPWGV QGPLTWQQFH KMAGRGSYGT DESPEPLPIP TFLLGYDYDY LVLSPFALPY WERLML EPY GSQRDIAYVV LCPENEALLN GAKSFFRDLT AIYESCRLGQ HRPVSRLLTD GIMRVGSTAS KKLSEKLVAE WFSQAAD GN NEAFSKLKLY AQVCRYDLGP YLASLPLDSS LLSQPNLVAP TSQSLITPPQ MTNTGNANTP SATLASAASS TMTVTSGV A ISTSVATANS TLTTASTSSS SSSNLNSGVS SNKLPSFPPF GSMNSNAAGS MSTQANTVQS GQLGGQQTSA LQTAGISGE SSSLPTQPHP DVSESTMDRD KVGIPTDGDS HAVTYPPAIV VYIIDPFTYE NTDESTNSSS VWTLGLLRCF LEMVQTLPPH IKSTVSVQI IPCQYLLQPV KHEDREIYPQ HLKSLAFSAF TQCRRPLPTS TNVKTLTGFG PGLAMETALR SPDRPECIRL Y APPFILAP VKDKQTELGE TFGEAGQKYN VLFVGYCLSH DQRWILASCT DLYGELLETC IINIDVPNRA RRKKSSARKF GL QKLWEWC LGLVQMSSLP WRVVIGRLGR IGHGELKDWS CLLSRRNLQS LSKRLKDMCR MCGISAADSP SILSACLVAM EPQ GSFVIM PDSVSTGSVF GRSTTLNMQT SQLNTPQDTS CTHILVFPTS ASVQVASATY TTENLDLAFN PNNDGADGMG IFDL LDTGD DLDPDIINIL PASPTGSPVH SPGSHYPHGG DAGKGQSTDR LLSTEPHEEV PNILQQPLAL GYFVSTAKAG PLPDW FWSA CPQAQYQCPL FLKASLHLHV PSVQSDELLH SKHSHPLDSN QTSDVLRFVL EQYNALSWLT CDPATQDRRS CLPIHF VVL NQLYNFIMNM L UniProtKB: Mediator of RNA polymerase II transcription subunit 13 |
-分子 #3: Cyclin-dependent kinase 8
分子 | 名称: Cyclin-dependent kinase 8 / タイプ: protein_or_peptide / ID: 3 / 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: 53.368668 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA LKQIEGTGIS MSACREIALL RELKHPNVIS LQKVFLSHA DRKVWLLFDY AEHDLWHIIK FHRASKANKK PVQLPRGMVK SLLYQILDGI HYLHANWVLH RDLKPANILV M GEGPERGR ...文字列: MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA LKQIEGTGIS MSACREIALL RELKHPNVIS LQKVFLSHA DRKVWLLFDY AEHDLWHIIK FHRASKANKK PVQLPRGMVK SLLYQILDGI HYLHANWVLH RDLKPANILV M GEGPERGR VKIADMGFAR LFNSPLKPLA DLDPVVVTFW YRAPELLLGA RHYTKAIDIW AIGCIFAELL TSEPIFHCRQ ED IKTSNPY HHDQLDRIFN VMGFPADKDW EDIKKMPEHS TLMKDFRRNT YTNCSLIKYM EKHKVKPDSK AFHLLQKLLT MDP IKRITS EQAMQDPYFL EDPLPTSDVF AGCQIPYPKR EFLTEEEPDD KGDKKNQQQQ QGNNHTNGTG HPGNQDSSHT QGPP LKKVR VVPPTTTSGG LIMTSDYQRS NPHAAYPNPG PSTSQPQSSM GYSATSQQPP QYSHQTHRY UniProtKB: Cyclin-dependent kinase 8 |
-分子 #4: Cyclin-C
分子 | 名称: Cyclin-C / 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: 33.279691 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MAGNFWQSSH YLQWILDKQD LLKERQKDLK FLSEEEYWKL QIFFTNVIQA LGEHLKLRQQ VIATATVYFK RFYARYSLKS IDPVLMAPT CVFLASKVEE FGVVSNTRLI AAATSVLKTR FSYAFPKEFP YRMNHILECE FYLLELMDCC LIVYHPYRPL L QYVQDMGQ ...文字列: MAGNFWQSSH YLQWILDKQD LLKERQKDLK FLSEEEYWKL QIFFTNVIQA LGEHLKLRQQ VIATATVYFK RFYARYSLKS IDPVLMAPT CVFLASKVEE FGVVSNTRLI AAATSVLKTR FSYAFPKEFP YRMNHILECE FYLLELMDCC LIVYHPYRPL L QYVQDMGQ EDMLLPLAWR IVNDTYRTDL CLLYPPFMIA LACLHVACVV QQKDARQWFA ELSVDMEKIL EIIRVILKLY EQ WKNFDER KEMATILSKM PKPKPPPNSE GEQGPNGSQN SSYSQS UniProtKB: Cyclin-C |
-分子 #5: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 5 / コピー数: 2 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-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
緩衝液 | pH: 7.9 |
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK III |
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電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) 平均電子線量: 64.0 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): 3.0 µm / 最小 デフォーカス(公称値): 0.6 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |