+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-27839 | |||||||||
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タイトル | Cryo-EM density of BIRC6/casp-3 (clusters) | |||||||||
マップデータ | main map / consensus | |||||||||
試料 |
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キーワード | Ubiquitin / E3 ligase / Apoptosis / Autophagy / IAP / LIGASE | |||||||||
機能・相同性 | 機能・相同性情報 spongiotrophoblast layer development / caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response / glial cell apoptotic process / labyrinthine layer development ...spongiotrophoblast layer development / caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response / glial cell apoptotic process / labyrinthine layer development / NADE modulates death signalling / luteolysis / response to cobalt ion / cysteine-type endopeptidase activity involved in apoptotic signaling pathway / death-inducing signaling complex / cellular response to staurosporine / ALK mutants bind TKIs / cyclin-dependent protein serine/threonine kinase inhibitor activity / Apoptosis induced DNA fragmentation / cysteine-type endopeptidase activity involved in execution phase of apoptosis / Caspase activation via Dependence Receptors in the absence of ligand / Apoptotic cleavage of cell adhesion proteins / death receptor binding / SMAC, XIAP-regulated apoptotic response / Flemming body / Activation of caspases through apoptosome-mediated cleavage / axonal fasciculation / Signaling by Hippo / cysteine-type endopeptidase activity involved in apoptotic process / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / fibroblast apoptotic process / microtubule organizing center / negative regulation of cytokine production / epithelial cell apoptotic process / platelet formation / execution phase of apoptosis / cysteine-type endopeptidase inhibitor activity / Other interleukin signaling / positive regulation of amyloid-beta formation / Apoptotic cleavage of cellular proteins / pyroptotic inflammatory response / negative regulation of B cell proliferation / T cell homeostasis / negative regulation of activated T cell proliferation / ubiquitin conjugating enzyme activity / B cell homeostasis / neurotrophin TRK receptor signaling pathway / protein maturation / negative regulation of cell cycle / response to X-ray / response to amino acid / Caspase-mediated cleavage of cytoskeletal proteins / cell fate commitment / regulation of macroautophagy / response to tumor necrosis factor / Pyroptosis / response to glucose / response to UV / response to glucocorticoid / keratinocyte differentiation / enzyme activator activity / striated muscle cell differentiation / Degradation of the extracellular matrix / intrinsic apoptotic signaling pathway / erythrocyte differentiation / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / hippocampus development / apoptotic signaling pathway / sensory perception of sound / response to nicotine / trans-Golgi network / RING-type E3 ubiquitin transferase / regulation of protein stability / protein catabolic process / response to hydrogen peroxide / neuron differentiation / protein processing / spindle pole / response to wounding / ubiquitin-protein transferase activity / positive regulation of neuron apoptotic process / Signaling by ALK fusions and activated point mutants / response to estradiol / heart development / peptidase activity / regulation of cell population proliferation / midbody / protease binding / neuron apoptotic process / cell population proliferation / response to lipopolysaccharide / aspartic-type endopeptidase activity / learning or memory / response to hypoxia / endosome / protein ubiquitination / response to xenobiotic stimulus / cell division 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: 2.82 Å | |||||||||
データ登録者 | Hunkeler M / Fischer ES | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Science / 年: 2023 タイトル: Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases. 著者: Moritz Hunkeler / Cyrus Y Jin / Eric S Fischer / 要旨: Tight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis ...Tight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis proteins (IAPs) are the principal actors that restrain caspase activity and are therefore attractive therapeutic targets. IAPs, in turn, are regulated by mitochondria-derived proapoptotic factors such as SMAC and HTRA2. Through a series of cryo-electron microscopy structures of full-length human baculoviral IAP repeat-containing protein 6 (BIRC6) bound to SMAC, caspases, and HTRA2, we provide a molecular understanding for BIRC6-mediated caspase inhibition and its release by SMAC. The architecture of BIRC6, together with near-irreversible binding of SMAC, elucidates how the IAP inhibitor SMAC can effectively control a processive ubiquitin ligase to respond to apoptotic stimuli. | |||||||||
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 | emd_27839.map.gz | 157.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-27839-v30.xml emd-27839.xml | 39.1 KB 39.1 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_27839_fsc.xml | 11.5 KB | 表示 | FSCデータファイル |
画像 | emd_27839.png | 109.3 KB | ||
マスクデータ | emd_27839_msk_1.map emd_27839_msk_2.map | 166.4 MB 52.7 MB | マスクマップ | |
Filedesc metadata | emd-27839.cif.gz | 9.4 KB | ||
その他 | emd_27839_additional_1.map.gz emd_27839_additional_2.map.gz emd_27839_additional_3.map.gz emd_27839_additional_4.map.gz emd_27839_additional_5.map.gz emd_27839_additional_6.map.gz emd_27839_half_map_1.map.gz emd_27839_half_map_2.map.gz | 157.1 MB 157.2 MB 157.2 MB 156.8 MB 157.1 MB 157.2 MB 154.2 MB 154.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-27839 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27839 | 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_27839.map.gz / 形式: CCP4 / 大きさ: 166.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | main map / consensus | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.2069 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
+追加マップ: cluster 1
+追加マップ: cluster 3
+追加マップ: cluster 2
+追加マップ: cluster 4
+追加マップ: cluster 5
+追加マップ: cluster 6
+ハーフマップ: half-map 2
+ハーフマップ: half-map 1
-試料の構成要素
-全体 : BIRC6/casp-3
全体 | 名称: BIRC6/casp-3 |
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要素 |
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-超分子 #1: BIRC6/casp-3
超分子 | 名称: BIRC6/casp-3 / 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) |
分子量 | 理論値: 1.132 MDa |
-分子 #1: Baculoviral IAP repeat-containing protein 6
分子 | 名称: Baculoviral IAP repeat-containing protein 6 / タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO / EC番号: 合成酵素 |
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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) |
配列 | 文字列: MGDWSHPQFE KSGGGSGGLE VLFQGPSRTM VTGGGAAPPG TVTEPLPSVI VLSAGRKMAA AAAAASGPGC SSAAGAGAAG VSEWLVLRDG CMHCDADGLH SLSYHPALNA ILAVTSRGTI KVIDGTSGAT LQASALSAKP GGQVKCQYIS AVDKVIFVDD YAVGCRKDLN ...文字列: MGDWSHPQFE KSGGGSGGLE VLFQGPSRTM VTGGGAAPPG TVTEPLPSVI VLSAGRKMAA AAAAASGPGC SSAAGAGAAG VSEWLVLRDG CMHCDADGLH SLSYHPALNA ILAVTSRGTI KVIDGTSGAT LQASALSAKP GGQVKCQYIS AVDKVIFVDD YAVGCRKDLN GILLLDTALQ TPVSKQDDVV QLELPVTEAQ QLLSACLEKV DISSTEGYDL FITQLKDGLK NTSHETAANH KVAKWATVTF HLPHHVLKSI ASAIVNELKK INQNVAALPV ASSVMDRLSY LLPSARPELG VGPGRSVDRS LMYSEANRRE TFTSWPHVGY RWAQPDPMAQ AGFYHQPASS GDDRAMCFTC SVCLVCWEPT DEPWSEHERH SPNCPFVKGE HTQNVPLSVT LATSPAQFPC TDGTDRISCF GSGSCPHFLA AATKRGKICI WDVSKLMKVH LKFEINAYDP AIVQQLILSG DPSSGVDSRR PTLAWLEDSS SCSDIPKLEG DSDDLLEDSD SEEHSRSDSV TGHTSQKEAM EVSLDITALS ILQQPEKLQW EIVANVLEDT VKDLEELGAN PCLTNSKSEK TKEKHQEQHN IPFPCLLAGG LLTYKSPATS PISSNSHRSL DGLSRTQGES ISEQGSTDNE SCTNSELNSP LVRRTLPVLL LYSIKESDEK AGKIFSQMNN IMSKSLHDDG FTVPQIIEME LDSQEQLLLQ DPPVTYIQQF ADAAANLTSP DSEKWNSVFP KPGTLVQCLR LPKFAEEENL CIDSITPCAD GIHLLVGLRT CPVESLSAIN QVEALNNLNK LNSALCNRRK GELESNLAVV NGANISVIQH ESPADVQTPL IIQPEQRNVS GGYLVLYKMN YATRIVTLEE EPIKIQHIKD PQDTITSLIL LPPDILDNRE DDCEEPIEDM QLTSKNGFER EKTSDISTLG HLVITTQGGY VKILDLSNFE ILAKVEPPKK EGTEEQDTFV SVIYCSGTDR LCACTKGGEL HFLQIGGTCD DIDEADILVD GSLSKGIEPS SEGSKPLSNP SSPGISGVDL LVDQPFTLEI LTSLVELTRF ETLTPRFSAT VPPCWVEVQQ EQQQRRHPQH LHQQHHGDAA QHTRTWKLQT DSNSWDEHVF ELVLPKACMV GHVDFKFVLN SNITNIPQIQ VTLLKNKAPG LGKVNALNIE VEQNGKPSLV DLNEEMQHMD VEESQCLRLC PFLEDHKEDI LCGPVWLASG LDLSGHAGML TLTSPKLVKG MAGGKYRSFL IHVKAVNERG TEEICNGGMR PVVRLPSLKH QSNKGYSLAS LLAKVAAGKE KSSNVKNENT SGTRKSENLR GCDLLQEVSV TIRRFKKTSI SKERVQRCAM LQFSEFHEKL VNTLCRKTDD GQITEHAQSL VLDTLCWLAG VHSNGPGSSK EGNENLLSKT RKFLSDIVRV CFFEAGRSIA HKCARFLALC ISNGKCDPCQ PAFGPVLLKA LLDNMSFLPA ATTGGSVYWY FVLLNYVKDE DLAGCSTACA SLLTAVSRQL QDRLTPMEAL LQTRYGLYSS PFDPVLFDLE MSGSSCKNVY NSSIGVQSDE IDLSDVLSGN GKVSSCTAAE GSFTSLTGLL EVEPLHFTCV STSDGTRIER DDAMSSFGVT PAVGGLSSGT VGEASTALSS AAQVALQSLS HAMASAEQQL QVLQEKQQQL LKLQQQKAKL EAKLHQTTAA AAAAASAVGP VHNSVPSNPV AAPGFFIHPS DVIPPTPKTT PLFMTPPLTP PNEAVSVVIN AELAQLFPGS VIDPPAVNLA AHNKNSNKSR MNPLGSGLAL AISHASHFLQ PPPHQSIIIE RMHSGARRFV TLDFGRPILL TDVLIPTCGD LASLSIDIWT LGEEVDGRRL VVATDISTHS LILHDLIPPP VCRFMKITVI GRYGSTNARA KIPLGFYYGH TYILPWESEL KLMHDPLKGE GESANQPEID QHLAMMVALQ EDIQCRYNLA CHRLETLLQS IDLPPLNSAN NAQYFLRKPD KAVEEDSRVF SAYQDCIQLQ LQLNLAHNAV QRLKVALGAS RKMLSETSNP EDLIQTSSTE QLRTIIRYLL DTLLSLLHAS NGHSVPAVLQ STFHAQACEE LFKHLCISGT PKIRLHTGLL LVQLCGGERW WGQFLSNVLQ ELYNSEQLLI FPQDRVFMLL SCIGQRSLSN SGVLESLLNL LDNLLSPLQP QLPMHRRTEG VLDIPMISWV VMLVSRLLDY VATVEDEAAA AKKPLNGNQW SFINNNLHTQ SLNRSSKGSS SLDRLYSRKI RKQLVHHKQQ LNLLKAKQKA LVEQMEKEKI QSNKGSSYKL LVEQAKLKQA TSKHFKDLIR LRRTAEWSRS NLDTEVTTAK ESPEIEPLPF TLAHERCISV VQKLVLFLLS MDFTCHADLL LFVCKVLARI ANATRPTIHL CEIVNEPQLE RLLLLLVGTD FNRGDISWGG AWAQYSLTCM LQDILAGELL APVAAEAMEE GTVGDDVGAT AGDSDDSLQQ SSVQLLETID EPLTHDITGA PPLSSLEKDK EIDLELLQDL MEVDIDPLDI DLEKDPLAAK VFKPISSTWY DYWGADYGTY NYNPYIGGLG IPVAKPPANT EKNGSQTVSV SVSQALDARL EVGLEQQAEL MLKMMSTLEA DSILQALTNT SPTLSQSPTG TDDSLLGGLQ AANQTSQLII QLSSVPMLNV CFNKLFSMLQ VHHVQLESLL QLWLTLSLNS SSTGNKENGA DIFLYNANRI PVISLNQASI TSFLTVLAWY PNTLLRTWCL VLHSLTLMTN MQLNSGSSSA IGTQESTAHL LVSDPNLIHV LVKFLSGTSP HGTNQHSPQV GPTATQAMQE FLTRLQVHLS STCPQIFSEF LLKLIHILST ERGAFQTGQG PLDAQVKLLE FTLEQNFEVV SVSTISAVIE SVTFLVHHYI TCSDKVMSRS GSDSSVGARA CFGGLFANLI RPGDAKAVCG EMTRDQLMFD LLKLVNILVQ LPLSGNREYS ARVSVTTNTT DSVSDEEKVS GGKDGNGSST SVQGSPAYVA DLVLANQQIM SQILSALGLC NSSAMAMIIG ASGLHLTKHE NFHGGLDAIS VGDGLFTILT TLSKKASTVH MMLQPILTYM ACGYMGRQGS LATCQLSEPL LWFILRVLDT SDALKAFHDM GGVQLICNNM VTSTRAIVNT ARSMVSTIMK FLDSGPNKAV DSTLKTRILA SEPDNAEGIH NFAPLGTITS SSPTAQPAEV LLQATPPHRR ARSAAWSYIF LPEEAWCDLT IHLPAAVLLK EIHIQPHLAS LATCPSSVSV EVSADGVNML PLSTPVVTSG LTYIKIQLVK AEVASAVCLR LHRPRDASTL GLSQIKLLGL TAFGTTSSAT VNNPFLPSED QVSKTSIGWL RLLHHCLTHI SDLEGMMASA AAPTANLLQT CAALLMSPYC GMHSPNIEVV LVKIGLQSTR IGLKLIDILL RNCAASGSDP TDLNSPLLFG RLNGLSSDST IDILYQLGTT QDPGTKDRIQ ALLKWVSDSA RVAAMKRSGR MNYMCPNSST VEYGLLMPSP SHLHCVAAIL WHSYELLVEY DLPALLDQEL FELLFNWSMS LPCNMVLKKA VDSLLCSMCH VHPNYFSLLM GWMGITPPPV QCHHRLSMTD DSKKQDLSSS LTDDSKNAQA PLALTESHLA TLASSSQSPE AIKQLLDSGL PSLLVRSLAS FCFSHISSSE SIAQSIDISQ DKLRRHHVPQ QCNKMPITAD LVAPILRFLT EVGNSHIMKD WLGGSEVNPL WTALLFLLCH SGSTSGSHNL GAQQTSARSA SLSSAATTGL TTQQRTAIEN ATVAFFLQCI SCHPNNQKLM AQVLCELFQT SPQRGNLPTS GNISGFIRRL FLQLMLEDEK VTMFLQSPCP LYKGRINATS HVIQHPMYGA GHKFRTLHLP VSTTLSDVLD RVSDTPSITA KLISEQKDDK EKKNHEEKEK VKAENGFQDN YSVVVASGLK SQSKRAVSAT PPRPPSRRGR TIPDKIGSTS GAEAANKIIT VPVFHLFHKL LAGQPLPAEM TLAQLLTLLY DRKLPQGYRS IDLTVKLGSR VITDPSLSKT DSYKRLHPEK DHGDLLASCP EDEALTPGDE CMDGILDESL LETCPIQSPL QVFAGMGGLA LIAERLPMLY PEVIQQVSAP VVTSTTQEKP KDSDQFEWVT IEQSGELVYE APETVAAEPP PIKSAVQTMS PIPAHSLAAF GLFLRLPGYA EVLLKERKHA QCLLRLVLGV TDDGEGSHIL QSPSANVLPT LPFHVLRSLF STTPLTTDDG VLLRRMALEI GALHLILVCL SALSHHSPRV PNSSVNQTEP QVSSSHNPTS TEEQQLYWAK GTGFGTGSTA SGWDVEQALT KQRLEEEHVT CLLQVLASYI NPVSSAVNGE AQSSHETRGQ NSNALPSVLL ELLSQSCLIP AMSSYLRNDS VLDMARHVPL YRALLELLRA IASCAAMVPL LLPLSTENGE EEEEQSECQT SVGTLLAKMK TCVDTYTNRL RSKRENVKTG VKPDASDQEP EGLTLLVPDI QKTAEIVYAA TTSLRQANQE KKLGEYSKKA AMKPKPLSVL KSLEEKYVAV MKKLQFDTFE MVSEDEDGKL GFKVNYHYMS QVKNANDANS AARARRLAQE AVTLSTSLPL SSSSSVFVRC DEERLDIMKV LITGPADTPY ANGCFEFDVY FPQDYPSSPP LVNLETTGGH SVRFNPNLYN DGKVCLSILN TWHGRPEEKW NPQTSSFLQV LVSVQSLILV AEPYFNEPGY ERSRGTPSGT QSSREYDGNI RQATVKWAML EQIRNPSPCF KEVIHKHFYL KRVEIMAQCE EWIADIQQYS SDKRVGRTMS HHAAALKRHT AQLREELLKL PCPEGLDPDT DDAPEVCRAT TGAEETLMHD QVKPSSSKEL PSDFQL UniProtKB: Baculoviral IAP repeat-containing protein 6 |
-分子 #2: Caspase-3
分子 | 名称: Caspase-3 / タイプ: protein_or_peptide / ID: 2 / 光学異性体: LEVO / EC番号: caspase-3 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MENTENSVDS KSIKNLEPKI IHGSESMDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG MTSRSGTDVD AANLRETFRN LKYEVRNKND LTREEIVELM RDVSKEDHSK RSSFVCVLLS HGEEGIIFGT NGPVDLKKIT NFFRGDRCRS LTGKPKLFII QACRGTELDC ...文字列: MENTENSVDS KSIKNLEPKI IHGSESMDSG ISLDNSYKMD YPEMGLCIII NNKNFHKSTG MTSRSGTDVD AANLRETFRN LKYEVRNKND LTREEIVELM RDVSKEDHSK RSSFVCVLLS HGEEGIIFGT NGPVDLKKIT NFFRGDRCRS LTGKPKLFII QACRGTELDC GIETDSGVDD DMACHKIPVE ADFLYAYSTA PGYYSWRNSK DGSWFIQSLC AMLKQYADKL EFMHILTRVN RKVATEFESF SFDATFHAKK QIPCIVSMLT KELYFYHLEH HHHHH UniProtKB: Caspase-3 |
-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
濃度 | 2 mg/mL | ||||||||||||
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緩衝液 | pH: 7.4 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 支持フィルム - Film thickness: 12 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 0.039 kPa | ||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 90 % / チャンバー内温度: 283.15 K / 装置: LEICA EM GP | ||||||||||||
詳細 | added CHAPSO to 0.4 mM |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 20 eV |
詳細 | Data collection in counting mode, using multi-shot scheme (9 holes per stage position, 2 movies per hole) |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 検出モード: COUNTING / デジタル化 - サイズ - 横: 5760 pixel / デジタル化 - サイズ - 縦: 4092 pixel / デジタル化 - 画像ごとのフレーム数: 1-50 / 撮影したグリッド数: 1 / 実像数: 10422 / 平均露光時間: 2.5 sec. / 平均電子線量: 51.401 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 50.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 105000 |
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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: OTHER |
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