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基本情報
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タイトル | Cryo-EM structure of CASTOR1 bound human GATOR2 complex | |||||||||
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![]() | amino acid sensor / SIGNALING PROTEIN | |||||||||
機能・相同性 | ![]() oligodendrocyte progenitor proliferation / GATOR2 complex / cellular response to L-arginine / molecular sensor activity / Seh1-associated complex / protein exit from endoplasmic reticulum / COPII-coated vesicle budding / central nervous system myelin formation / COPII-coated vesicle cargo loading / nuclear pore outer ring ...oligodendrocyte progenitor proliferation / GATOR2 complex / cellular response to L-arginine / molecular sensor activity / Seh1-associated complex / protein exit from endoplasmic reticulum / COPII-coated vesicle budding / central nervous system myelin formation / COPII-coated vesicle cargo loading / nuclear pore outer ring / nuclear pore organization / COPII vesicle coat / Nuclear Pore Complex (NPC) Disassembly / Transport of Ribonucleoproteins into the Host Nucleus / Regulation of Glucokinase by Glucokinase Regulatory Protein / Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) / Amino acids regulate mTORC1 / protein K6-linked ubiquitination / attachment of mitotic spindle microtubules to kinetochore / Transport of the SLBP independent Mature mRNA / NS1 Mediated Effects on Host Pathways / Transport of the SLBP Dependant Mature mRNA / SUMOylation of SUMOylation proteins / protein-containing complex localization / Transport of Mature mRNA Derived from an Intronless Transcript / Rev-mediated nuclear export of HIV RNA / Nuclear import of Rev protein / SUMOylation of RNA binding proteins / NEP/NS2 Interacts with the Cellular Export Machinery / arginine binding / Transport of Mature mRNA derived from an Intron-Containing Transcript / tRNA processing in the nucleus / Postmitotic nuclear pore complex (NPC) reformation / COPII-mediated vesicle transport / vacuolar membrane / nucleocytoplasmic transport / Viral Messenger RNA Synthesis / mitotic metaphase chromosome alignment / SUMOylation of ubiquitinylation proteins / Vpr-mediated nuclear import of PICs / oligodendrocyte differentiation / SUMOylation of DNA replication proteins / positive regulation of macroautophagy / positive regulation of TOR signaling / Regulation of HSF1-mediated heat shock response / mRNA transport / nuclear pore / SUMOylation of DNA damage response and repair proteins / cellular response to nutrient levels / negative regulation of TORC1 signaling / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / signaling adaptor activity / positive regulation of TORC1 signaling / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / MHC class II antigen presentation / cellular response to amino acid starvation / protein sequestering activity / Resolution of Sister Chromatid Cohesion / SUMOylation of chromatin organization proteins / HCMV Late Events / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / intracellular protein transport / Transcriptional regulation by small RNAs / ISG15 antiviral mechanism / RHO GTPases Activate Formins / ER to Golgi transport vesicle membrane / RING-type E3 ubiquitin transferase / kinetochore / autophagy / Separation of Sister Chromatids / HCMV Early Events / protein import into nucleus / ubiquitin protein ligase activity / cell junction / nuclear envelope / protein transport / snRNP Assembly / regulation of autophagy / defense response to Gram-positive bacterium / lysosomal membrane / cell division / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / extracellular exosome / zinc ion binding / nucleoplasm / identical protein binding / cytosol / cytoplasm 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: 3.59 Å | |||||||||
![]() | Su M-Y | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Cryo-EM structures of amino acid sensors bound to the human GATOR2 complex. 著者: Ming-Yuan Su / Fei Teng / Shan Wang / Xinyi Mai / Huan Zeng / Juan Li / Xiaoxiao Song / Xi Wang / Goran Stjepanovic / ![]() 要旨: Mammalian cells regulate growth by integrating environmental cues through the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The human GATOR2 complex, comprising WDR59, WDR24, ...Mammalian cells regulate growth by integrating environmental cues through the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The human GATOR2 complex, comprising WDR59, WDR24, Mios, Sec13, and Seh1l, is key to mTORC1 regulation. Under amino acid deprivation, GATOR2 is inhibited through interactions with cytosolic leucine sensor Sestrin2 and arginine sensor cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1). Amino acid abundance relieves this inhibition, allowing GATOR2 to antagonize the repressor GATOR1. Despite its importance, GATOR2's inhibition mechanisms were unclear. Here, we present cryo-electron microscopy (cryo-EM) structures of GATOR2 in three inhibitory states: CASTOR1 bound, Sestrin2 bound, and dual bound. CASTOR1 engages the Mios WD40 β-propellers, while Sestrin2 interacts with the WDR24-Seh1l subcomplex, inducing conformational movements. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) reveals dynamic motions in apo-GATOR2 and its complexes with amino acid sensors, as well as the effects of amino acid supplementation. These findings unravel the interactions between GATOR2 and amino acid sensors, providing a perspective on the regulation of the mTORC1 pathway by nutrient-sensing machinery. | |||||||||
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構造の表示
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画像 | ![]() | 47.2 KB | ||
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Filedesc metadata | ![]() | 8.9 KB | ||
その他 | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 656.4 MB 369.2 MB 2 MB 369.6 MB 369.9 MB 368 MB 369.3 MB 371.1 MB 368.6 MB 369.6 MB 689.9 MB 689.9 MB | ||
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文書・要旨 | ![]() | 984.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 984.4 KB | 表示 | |
XML形式データ | ![]() | 19.8 KB | 表示 | |
CIF形式データ | ![]() | 23.9 KB | 表示 | |
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「今月の分子」の関連する項目 |
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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: 0.85 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
+マスク #2
+マスク #3
+マスク #4
+マスク #5
+マスク #6
+マスク #7
+追加マップ: #10
+追加マップ: #1
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試料の構成要素
-全体 : Cryo-EM structure of CASTOR1 bound human GATOR2 complex
全体 | 名称: Cryo-EM structure of CASTOR1 bound human GATOR2 complex |
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要素 |
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-超分子 #1: Cryo-EM structure of CASTOR1 bound human GATOR2 complex
超分子 | 名称: Cryo-EM structure of CASTOR1 bound human GATOR2 complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: ![]() |
-分子 #1: GATOR2 complex protein MIOS
分子 | 名称: GATOR2 complex protein MIOS / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 98.700391 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSGTKPDILW APHHVDRFVV CDSELSLYHV ESTVNSELKA GSLRLSEDSA ATLLSINSDT PYMKCVAWYL NYDPECLLAV GQANGRVVL TSLGQDHNSK FKDLIGKEFV PKHARQCNTL AWNPLDSNWL AAGLDKHRAD FSVLIWDICS KYTPDIVPME K VKLSAGET ...文字列: MSGTKPDILW APHHVDRFVV CDSELSLYHV ESTVNSELKA GSLRLSEDSA ATLLSINSDT PYMKCVAWYL NYDPECLLAV GQANGRVVL TSLGQDHNSK FKDLIGKEFV PKHARQCNTL AWNPLDSNWL AAGLDKHRAD FSVLIWDICS KYTPDIVPME K VKLSAGET ETTLLVTKPL YELGQNDACL SLCWLPRDQK LLLAGMHRNL AIFDLRNTSQ KMFVNTKAVQ GVTVDPYFHD RV ASFYEGQ VAIWDLRKFE KPVLTLTEQP KPLTKVAWCP TRTGLLATLT RDSNIIRLYD MQHTPTPIGD ETEPTIIERS VQP CDNYIA SFAWHPTSQN RMIVVTPNRT MSDFTVFERI SLAWSPITSL MWACGRHLYE CTEEENDNSL EKDIATKMRL RALS RYGLD TEQVWRNHIL AGNEDPQLKS LWYTLHFMKQ YTEDMDQKSP GNKGSLVYAG IKSIVKSSLG MVESSRHNWS GLDKQ SDIQ NLNEERILAL QLCGWIKKGT DVDVGPFLNS LVQEGEWERA AAVALFNLDI RRAIQILNEG ASSEKGDLNL NVVAMA LSG YTDEKNSLWR EMCSTLRLQL NNPYLCVMFA FLTSETGSYD GVLYENKVAV RDRVAFACKF LSDTQLNRYI EKLTNEM KE AGNLEGILLT GLTKDGVDLM ESYVDRTGDV QTASYCMLQG SPLDVLKDER VQYWIENYRN LLDAWRFWHK RAEFDIHR S KLDPSSKPLA QVFVSCNFCG KSISYSCSAV PHQGRGFSQY GVSGSPTKSK VTSCPGCRKP LPRCALCLIN MGTPVSSCP GGTKSDEKVD LSKDKKLAQF NNWFTWCHNC RHGGHAGHML SWFRDHAECP VSACTCKCMQ LDTTGNLVPA ETVQP UniProtKB: GATOR2 complex protein MIOS |
-分子 #2: GATOR2 complex protein WDR24
分子 | 名称: GATOR2 complex protein WDR24 / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 88.326953 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MEKMSRVTTA LGGSVLTGRT MHCHLDAPAN AISVCRDAAQ VVVAGRSIFK IYAIEEEQFV EKLNLRVGRK PSLNLSCADV VWHQMDENL LATAATNGVV VTWNLGRPSR NKQDQLFTEH KRTVNKVCFH PTEAHVLLSG SQDGFMKCFD LRRKDSVSTF S GQSESVRD ...文字列: MEKMSRVTTA LGGSVLTGRT MHCHLDAPAN AISVCRDAAQ VVVAGRSIFK IYAIEEEQFV EKLNLRVGRK PSLNLSCADV VWHQMDENL LATAATNGVV VTWNLGRPSR NKQDQLFTEH KRTVNKVCFH PTEAHVLLSG SQDGFMKCFD LRRKDSVSTF S GQSESVRD VQFSIRDYFT FASTFENGNV QLWDIRRPDR CERMFTAHNG PVFCCDWHPE DRGWLATGGR DKMVKVWDMT TH RAKEMHC VQTIASVARV KWRPECRHHL ATCSMMVDHN IYVWDVRRPF VPAAMFEEHR DVTTGIAWRH PHDPSFLLSG SKD SSLCQH LFRDASQPVE RANPEGLCYG LFGDLAFAAK ESLVAAESGR KPYTGDRRHP IFFKRKLDPA EPFAGLASSA LSVF ETEPG GGGMRWFVDT AERYALAGRP LAELCDHNAK VARELGRNQV AQTWTMLRII YCSPGLVPTA NLNHSVGKGG SCGLP LMNS FNLKDMAPGL GSETRLDRSK GDARSDTVLL DSSATLITNE DNEETEGSDV PADYLLGDVE GEEDELYLLD PEHAHP EDP ECVLPQEAFP LRHEIVDTPP GPEHLQDKAD SPHVSGSEAD VASLAPVDSS FSLLSVSHAL YDSRLPPDFF GVLVRDM LH FYAEQGDVQM AVSVLIVLGE RVRKDIDEQT QEHWYTSYID LLQRFRLWNV SNEVVKLSTS RAVSCLNQAS TTLHVNCS H CKRPMSSRGW VCDRCHRCAS MCAVCHHVVK GLFVWCQGCS HGGHLQHIMK WLEGSSHCPA GCGHLCEYS UniProtKB: GATOR2 complex protein WDR24 |
-分子 #3: GATOR2 complex protein WDR59
分子 | 名称: GATOR2 complex protein WDR59 / タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 109.938391 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MAARWSSENV VVEFRDSQAT AMSVDCLGQH AVLSGRRFLY IVNLDAPFEG HRKISRQSKW DIGAVQWNPH DSFAHYFAAS SNQRVDLYK WKDGSGEVGT TLQGHTRVIS DLDWAVFEPD LLVTSSVDTY IYIWDIKDTR KPTVALSAVA GASQVKWNKK N ANCLATSH ...文字列: MAARWSSENV VVEFRDSQAT AMSVDCLGQH AVLSGRRFLY IVNLDAPFEG HRKISRQSKW DIGAVQWNPH DSFAHYFAAS SNQRVDLYK WKDGSGEVGT TLQGHTRVIS DLDWAVFEPD LLVTSSVDTY IYIWDIKDTR KPTVALSAVA GASQVKWNKK N ANCLATSH DGDVRIWDKR KPSTAVEYLA AHLSKIHGLD WHPDSEHILA TSSQDNSVKF WDYRQPRKYL NILPCQVPVW KA RYTPFSN GLVTVMVPQL RRENSLLLWN VFDLNTPVHT FVGHDDVVLE FQWRKQKEGS KDYQLVTWSR DQTLRMWRVD SQM QRLCAN DILDGVDEFI ESISLLPEPE KTLHTEDTDH QHTASHGEEE ALKEDPPRNL LEERKSDQLG LPQTLQQEFS LINV QIRNV NVEMDAADRS CTVSVHCSNH RVKMLVKFPA QYPNNAAPSF QFINPTTITS TMKAKLLKIL KDTALQKVKR GQSCL EPCL RQLVSCLESF VNQEDSASSN PFALPNSVTP PLPTFARVTT AYGSYQDANI PFPRTSGARF CGAGYLVYFT RPMTMH RAV SPTEPTPRSL SALSAYHTGL IAPMKIRTEA PGNLRLYSGS PTRSEKEQVS ISSFYYKERK SRRWKSKREG SDSGNRQ IK AAGKVIIQDI ACLLPVHKSL GELYILNVND IQETCQKNAA SALLVGRKDL VQVWSLATVA TDLCLGPKSD PDLETPWA R HPFGRQLLES LLAHYCRLRD VQTLAMLCSV FEAQSRPQGL PNPFGPFPNR SSNLVVSHSR YPSFTSSGSC SSMSDPGLN TGGWNIAGRE AEHLSSPWGE SSPEELRFGS LTYSDPRERE RDQHDKNKRL LDPANTQQFD DFKKCYGEIL YRWGLREKRA EVLKFVSCP PDPHKGIEFG VYCSHCRSEV RGTQCAICKG FTFQCAICHV AVRGSSNFCL TCGHGGHTSH MMEWFRTQEV C PTGCGCHC LLESTF UniProtKB: GATOR2 complex protein WDR59 |
-分子 #4: Isoform B of Nucleoporin SEH1
分子 | 名称: Isoform B of Nucleoporin SEH1 / タイプ: protein_or_peptide / ID: 4 / コピー数: 6 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 46.636289 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MFVARSIAAD HKDLIHDVSF DFHGRRMATC SSDQSVKVWD KSESGDWHCT ASWKTHSGSV WRVTWAHPEF GQVLASCSFD RTAAVWEEI VGESNDKLRG QSHWVKRTTL VDSRTSVTDV KFAPKHMGLM LATCSADGIV RIYEAPDVMN LSQWSLQHEI S CKLSCSCI ...文字列: MFVARSIAAD HKDLIHDVSF DFHGRRMATC SSDQSVKVWD KSESGDWHCT ASWKTHSGSV WRVTWAHPEF GQVLASCSFD RTAAVWEEI VGESNDKLRG QSHWVKRTTL VDSRTSVTDV KFAPKHMGLM LATCSADGIV RIYEAPDVMN LSQWSLQHEI S CKLSCSCI SWNPSSSRAH SPMIAVGSDD SSPNAMAKVQ IFEYNENTRK YAKAETLMTV TDPVHDIAFA PNLGRSFHIL AI ATKDVRI FTLKPVRKEL TSSGGPTKFE IHIVAQFDNH NSQVWRVSWN ITGTVLASSG DDGCVRLWKA NYMDNWKCTG ILK GNGSPV NGSSQQGTSN PSLGSTIPSL QNSLNGSSAG RYFFTPLDSP RAGSRWSSYA QLLPPPPPPL VEHSCDADTA NLQY PHPRR RYLSRPLNPL PENEGI UniProtKB: Nucleoporin SEH1 |
-分子 #5: Isoform 3 of Protein SEC13 homolog
分子 | 名称: Isoform 3 of Protein SEC13 homolog / タイプ: protein_or_peptide / ID: 5 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 40.791668 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MREPVLTWCV PLELLCSHPL PLSAFLKSQV KLYTYRACAG KDEMGKMVSV INTVDTSHED MIHDAQMDYY GTRLATCSSD RSVKIFDVR NGGQILIADL RGHEGPVWQV AWAHPMYGNI LASCSYDRKV IIWREENGTW EKSHEHAGHD SSVNSVCWAP H DYGLILAC ...文字列: MREPVLTWCV PLELLCSHPL PLSAFLKSQV KLYTYRACAG KDEMGKMVSV INTVDTSHED MIHDAQMDYY GTRLATCSSD RSVKIFDVR NGGQILIADL RGHEGPVWQV AWAHPMYGNI LASCSYDRKV IIWREENGTW EKSHEHAGHD SSVNSVCWAP H DYGLILAC GSSDGAISLL TYTGEGQWEV KKINNAHTIG CNAVSWAPAV VPGSLIDHPS GQKPNYIKRF ASGGCDNLIK LW KEEEDGQ WKEEQKLEAH SDWVRDVAWA PSIGLPTSTI ASCSQDGRVF IWTCDDASSN TWSPKLLHKF NDVVWHVSWS ITA NILAVS GGDNKVTLWK ESVDGQWVCI SDVNKGQGSV SASVTEGQQN EQ UniProtKB: Protein SEC13 homolog |
-分子 #6: Cytosolic arginine sensor for mTORC1 subunit 1
分子 | 名称: Cytosolic arginine sensor for mTORC1 subunit 1 / タイプ: protein_or_peptide / ID: 6 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 36.265234 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MELHILEHRV RVLSVARPGL WLYTHPLIKL LFLPRRSRCK FFSLTETPED YTLMVDEEGF KELPPSEFLQ VAEATWLVLN VSSHSGAAV QAAGVTKIAR SVIAPLAEHH VSVLMLSTYQ TDFILVREQD LSVVIHTLAQ EFDIYREVGG EPVPVTRDDS S NGFPRTQH ...文字列: MELHILEHRV RVLSVARPGL WLYTHPLIKL LFLPRRSRCK FFSLTETPED YTLMVDEEGF KELPPSEFLQ VAEATWLVLN VSSHSGAAV QAAGVTKIAR SVIAPLAEHH VSVLMLSTYQ TDFILVREQD LSVVIHTLAQ EFDIYREVGG EPVPVTRDDS S NGFPRTQH GPSPTVHPIQ SPQNRFCVLT LDPETLPAIA TTLIDVLFYS HSTPKEAASS SPEPSSITFF AFSLIEGYIS IV MDAETQK KFPSDLLLTS SSGELWRMVR IGGQPLGFDE CGIVAQIAGP LAAADISAYY ISTFNFAHAL VPEDGIGSVI EVL QRRQEG LAS UniProtKB: Cytosolic arginine sensor for mTORC1 subunit 1 |
-分子 #7: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 7 / コピー数: 31 / 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: 7.4 |
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凍結 | 凍結剤: ETHANE |
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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 K3 (6k x 4k) / 平均電子線量: 51.52 e/Å2 詳細: The total dose on the specimen was 51.52, 51.87, 49,72, 46.79, 47.65, 48.04 and 48.04 e-/A2 fractionated over 50 frames |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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): 1.8 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |