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基本情報
登録情報 | データベース: EMDB / ID: EMD-23021 | |||||||||
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タイトル | Cryo-EM structure of PRC2:EZH1-AEBP2-JARID2 | |||||||||
![]() | Cryo-EM structure of PRC2:EZH1-AEBP2-JARID2 | |||||||||
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![]() | Chromatin / methyltransferase / nucleosome-modifying complex / GENE REGULATION / GENE REGULATION-Transferase complex | |||||||||
機能・相同性 | ![]() protein localization to pericentric heterochromatin / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / ubiquitin-modified histone reader activity / facultative heterochromatin formation / histone H3K27 methyltransferase activity / negative regulation of cardiac muscle hypertrophy ...protein localization to pericentric heterochromatin / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / ubiquitin-modified histone reader activity / facultative heterochromatin formation / histone H3K27 methyltransferase activity / negative regulation of cardiac muscle hypertrophy / negative regulation of cardiac muscle cell proliferation / NURF complex / regulation of cell fate specification / negative regulation of stem cell population maintenance / DNA replication-dependent chromatin assembly / chromatin silencing complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of stem cell differentiation / NuRD complex / ESC/E(Z) complex / Transcription of E2F targets under negative control by DREAM complex / RSC-type complex / Polo-like kinase mediated events / lncRNA binding / cardiac muscle cell proliferation / histone methyltransferase complex / spinal cord development / Sin3-type complex / positive regulation of stem cell population maintenance / histone methyltransferase activity / G1/S-Specific Transcription / ATPase complex / oligodendrocyte differentiation / Transcriptional Regulation by E2F6 / RNA Polymerase I Transcription Initiation / negative regulation of cell differentiation / histone deacetylase complex / G0 and Early G1 / subtelomeric heterochromatin formation / anatomical structure morphogenesis / heterochromatin / heterochromatin formation / Cyclin E associated events during G1/S transition / Cyclin A:Cdk2-associated events at S phase entry / nucleosome binding / Deposition of new CENPA-containing nucleosomes at the centromere / spleen development / enzyme activator activity / Regulation of TP53 Activity through Acetylation / methylated histone binding / SUMOylation of chromatin organization proteins / negative regulation of cell migration / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / thymus development / molecular condensate scaffold activity / liver development / PRC2 methylates histones and DNA / Regulation of PTEN gene transcription / ubiquitin binding / Defective pyroptosis / cellular response to leukemia inhibitory factor / central nervous system development / HDACs deacetylate histones / stem cell differentiation / hippocampus development / promoter-specific chromatin binding / transcription coregulator activity / negative regulation of transforming growth factor beta receptor signaling pathway / brain development / chromatin DNA binding / PKMTs methylate histone lysines / histone deacetylase binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / transcription corepressor activity / nucleosome assembly / chromatin organization / chromosome / histone binding / methylation / regulation of gene expression / Oxidative Stress Induced Senescence / DNA replication / cell population proliferation / Potential therapeutics for SARS / chromosome, telomeric region / nuclear body / chromatin remodeling / ribonucleoprotein complex / cell cycle / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of cell population proliferation / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / chromatin / nucleolus / regulation of transcription by RNA polymerase II 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: 3.9 Å | |||||||||
![]() | Grau DJ / Armache KJ | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction. 著者: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz ...著者: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz / Karim-Jean Armache / ![]() ![]() 要旨: Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the ...Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the selective incorporation of one of two paralogs of the catalytic subunit, EZH1 or EZH2. Each of these enzymes has specialized biological functions that may be partially explained by differences in the multivalent interactions they mediate with chromatin. Here, we present two cryo-EM structures of PRC2:EZH1, one as a monomer and a second one as a dimer bound to a nucleosome. When bound to nucleosome substrate, the PRC2:EZH1 dimer undergoes a dramatic conformational change. We demonstrate that mutation of a divergent EZH1/2 loop abrogates the nucleosome-binding and methyltransferase activities of PRC2:EZH1. Finally, we show that PRC2:EZH1 dimers are more effective than monomers at promoting chromatin compaction, and the divergent EZH1/2 loop is essential for this function, thereby tying together the methyltransferase, nucleosome-binding, and chromatin-compaction activities of PRC2:EZH1. We speculate that the conformational flexibility and the ability to dimerize enable PRC2 to act on the varied chromatin substrates it encounters in the cell. | |||||||||
履歴 |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 20.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.1 KB 20.1 KB | 表示 表示 | ![]() |
画像 | ![]() | 96.4 KB | ||
Filedesc metadata | ![]() | 8.2 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 541.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 541.4 KB | 表示 | |
XML形式データ | ![]() | 5.5 KB | 表示 | |
CIF形式データ | ![]() | 6.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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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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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Cryo-EM structure of PRC2:EZH1-AEBP2-JARID2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.3 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
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試料の構成要素
-全体 : PRC2:EZH1-AEBP2-JARID2
全体 | 名称: PRC2:EZH1-AEBP2-JARID2 |
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要素 |
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-超分子 #1: PRC2:EZH1-AEBP2-JARID2
超分子 | 名称: PRC2:EZH1-AEBP2-JARID2 / 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: ![]() |
分子量 | 理論値: 330 KDa |
-分子 #1: Histone-lysine N-methyltransferase EZH1
分子 | 名称: Histone-lysine N-methyltransferase EZH1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: [histone H3]-lysine27 N-trimethyltransferase |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 85.394141 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MEIPNPPTSK CITYWKRKVK SEYMRLRQLK RLQANMGAKA LYVANFAKVQ EKTQILNEEW KKLRVQPVQS MKPVSGHPFL KKCTIESIF PGFASQHMLM RSLNTVALVP IMYSWSPLQQ NFMVEDETVL CNIPYMGDEV KEEDETFIEE LINNYDGKVH G EEEMIPGS ...文字列: MEIPNPPTSK CITYWKRKVK SEYMRLRQLK RLQANMGAKA LYVANFAKVQ EKTQILNEEW KKLRVQPVQS MKPVSGHPFL KKCTIESIF PGFASQHMLM RSLNTVALVP IMYSWSPLQQ NFMVEDETVL CNIPYMGDEV KEEDETFIEE LINNYDGKVH G EEEMIPGS VLISDAVFLE LVDALNQYSD EEEEGHNDTS DGKQDDSKED LPVTRKRKRH AIEGNKKSSK KQFPNDMIFS AI ASMFPEN GVPDDMKERY RELTEMSDPN ALPPQCTPNI DGPNAKSVQR EQSLHSFHTL FCRRCFKYDC FLHPFHATPN VYK RKNKEI KIEPEPCGTD CFLLLEGAKE YAMLHNPRSK CSGRRRRRHH IVSASCSNAS ASAVAETKEG DSDRDTGNDW ASSS SEANS RCQTPTKQKA SPAPPQLCVV EAPSEPVEWT GAEESLFRVF HGTYFNNFCS IARLLGTKTC KQVFQFAVKE SLILK LPTD ELMNPSQKKK RKHRLWAAHC RKIQLKKDNS STQVYNYQPC DHPDRPCDST CPCIMTQNFC EKFCQCNPDC QNRFPG CRC KTQCNTKQCP CYLAVRECDP DLCLTCGASE HWDCKVVSCK NCSIQRGLKK HLLLAPSDVA GWGTFIKESV QKNEFIS EY CGELISQDEA DRRGKVYDKY MSSFLFNLNN DFVVDATRKG NKIRFANHSV NPNCYAKVVM VNGDHRIGIF AKRAIQAG E ELFFDYRYSQ ADALKYVGIE RETDVL UniProtKB: Histone-lysine N-methyltransferase EZH1 |
-分子 #2: Polycomb protein EED
分子 | 名称: Polycomb protein EED / 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: 50.267691 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP NAPGRKSWGK GKWKSKKCKY SFKCVNSLK EDHNQPLFGV QFNWHSKEGD PLVFATVGSN RVTLYECHSQ GEIRLLQSYV DADADENFYT CAWTYDSNTS H PLLAVAGS ...文字列: MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP NAPGRKSWGK GKWKSKKCKY SFKCVNSLK EDHNQPLFGV QFNWHSKEGD PLVFATVGSN RVTLYECHSQ GEIRLLQSYV DADADENFYT CAWTYDSNTS H PLLAVAGS RGIIRIINPI TMQCIKHYVG HGNAINELKF HPRDPNLLLS VSKDHALRLW NIQTDTLVAI FGGVEGHRDE VL SADYDLL GEKIMSCGMD HSLKLWRINS KRMMNAIKES YDYNPNKTNR PFISQKIHFP DFSTRDIHRN YVDCVRWLGD LIL SKSCEN AIVCWKPGKM EDDIDKIKPS ESNVTILGRF DYSQCDIWYM RFSMDFWQKM LALGNQVGKL YVWDLEVEDP HKAK CTTLT HHKCGAAIRQ TSFSRDSSIL IAVCDDASIW RWDRLR UniProtKB: Polycomb protein EED |
-分子 #3: Polycomb protein SUZ12
分子 | 名称: Polycomb protein SUZ12 / 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: 83.181922 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MAPQKHGGGG GGGSGPSAGS GGGGFGGSAA VAAATASGGK SGGGSCGGGG SYSASSSSSA AAAAGAAVLP VKKPKMEHVQ ADHELFLQA FEKPTQIYRF LRTRNLIAPI FLHRTLTYMS HRNSRTNIKR KTFKVDDMLS KVEKMKGEQE SHSLSAHLQL T FTGFFHKN ...文字列: MAPQKHGGGG GGGSGPSAGS GGGGFGGSAA VAAATASGGK SGGGSCGGGG SYSASSSSSA AAAAGAAVLP VKKPKMEHVQ ADHELFLQA FEKPTQIYRF LRTRNLIAPI FLHRTLTYMS HRNSRTNIKR KTFKVDDMLS KVEKMKGEQE SHSLSAHLQL T FTGFFHKN DKPSPNSENE QNSVTLEVLL VKVCHKKRKD VSCPIRQVPT GKKQVPLNPD LNQTKPGNFP SLAVSSNEFE PS NSHMVKS YSLLFRVTRP GRREFNGMIN GETNENIDVN EELPARRKRN REDGEKTFVA QMTVFDKNRR LQLLDGEYEV AMQ EMEECP ISKKRATWET ILDGKRLPPF ETFSQGPTLQ FTLRWTGETN DKSTAPIAKP LATRNSESLH QENKPGSVKP TQTI AVKES LTTDLQTRKE KDTPNENRQK LRIFYQFLYN NNTRQQTEAR DDLHCPWCTL NCRKLYSLLK HLKLCHSRFI FNYVY HPKG ARIDVSINEC YDGSYAGNPQ DIHRQPGFAF SRNGPVKRTP ITHILVCRPK RTKASMSEFL ESEDGEVEQQ RTYSSG HNR LYFHSDTCLP LRPQEMEVDS EDEKDPEWLR EKTITQIEEF SDVNEGEKEV MKLWNLHVMK HGFIADNQMN HACMLFV EN YGQKIIKKNL CRNFMLHLVS MHDFNLISIM SIDKAVTKLR EMQQKLEKGE SASPANEEIT EEQNGTANGF SEINSKEK A LETDSVSGVS KQSKKQKL UniProtKB: Polycomb protein SUZ12 |
-分子 #4: Histone-binding protein RBBP4
分子 | 名称: Histone-binding protein RBBP4 / 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: 47.709527 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MADKEAAFDD AVEERVINEE YKIWKKNTPF LYDLVMTHAL EWPSLTAQWL PDVTRPEGKD FSIHRLVLGT HTSDEQNHLV IASVQLPND DAQFDASHYD SEKGEFGGFG SVSGKIEIEI KINHEGEVNR ARYMPQNPCI IATKTPSSDV LVFDYTKHPS K PDPSGECN ...文字列: MADKEAAFDD AVEERVINEE YKIWKKNTPF LYDLVMTHAL EWPSLTAQWL PDVTRPEGKD FSIHRLVLGT HTSDEQNHLV IASVQLPND DAQFDASHYD SEKGEFGGFG SVSGKIEIEI KINHEGEVNR ARYMPQNPCI IATKTPSSDV LVFDYTKHPS K PDPSGECN PDLRLRGHQK EGYGLSWNPN LSGHLLSASD DHTICLWDIS AVPKEGKVVD AKTIFTGHTA VVEDVSWHLL HE SLFGSVA DDQKLMIWDT RSNNTSKPSH SVDAHTAEVN CLSFNPYSEF ILATGSADKT VALWDLRNLK LKLHSFESHK DEI FQVQWS PHNETILASS GTDRRLNVWD LSKIGEEQSP EDAEDGPPEL LFIHGGHTAK ISDFSWNPNE PWVICSVSED NIMQ VWQMA ENIYNDEDPE GSVDPEGQGS UniProtKB: Histone-binding protein RBBP4 |
-分子 #5: Zinc finger protein AEBP2
分子 | 名称: Zinc finger protein AEBP2 / 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: 33.012668 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSSDGEPLSR MDSEDSISST IMDVDSTISS GRSTPAMMNG QGSTTSSSKN IAYNCCWDQC QACFNSSPDL ADHIRSIHVD GQRGGVFVC LWKGCKVYNT PSTSQSWLQR HMLTHSGDKP FKCVVGGCNA SFASQGGLAR HVPTHFSQQN SSKVSSQPKA K EESPSKAG ...文字列: MSSDGEPLSR MDSEDSISST IMDVDSTISS GRSTPAMMNG QGSTTSSSKN IAYNCCWDQC QACFNSSPDL ADHIRSIHVD GQRGGVFVC LWKGCKVYNT PSTSQSWLQR HMLTHSGDKP FKCVVGGCNA SFASQGGLAR HVPTHFSQQN SSKVSSQPKA K EESPSKAG MNKRRKLKNK RRRSLPRPHD FFDAQTLDAI RHRAICFNLS AHIESLGKGH SVVFHSTVIA KRKEDSGKIK LL LHWMPED ILPDVWVNES ERHQLKTKVV HLSKLPKDTA LLLDPNIYRT MPQKRLKR UniProtKB: Zinc finger protein AEBP2 |
-分子 #6: Protein Jumonji
分子 | 名称: Protein Jumonji / 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: 138.979719 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSKERPKRNI IQKKYDDSDG IPWSEERVVR KVLYLSLKEF KNSQKRQHAE GIAGSLKTVN GLLGNDQSKG LGPASEQSEN EKDDASQVS STSNDVSSSD FEEGPSRKRP RLQAQRKFAQ SQPNSPSTTP VKIVEPLLPP PATQISDLSK RKPKTEDFLT F LCLRGSPA ...文字列: MSKERPKRNI IQKKYDDSDG IPWSEERVVR KVLYLSLKEF KNSQKRQHAE GIAGSLKTVN GLLGNDQSKG LGPASEQSEN EKDDASQVS STSNDVSSSD FEEGPSRKRP RLQAQRKFAQ SQPNSPSTTP VKIVEPLLPP PATQISDLSK RKPKTEDFLT F LCLRGSPA LPNSMVYFGS SQDEEEVEEE DDETEDVKTA TNNASSSCQS TPRKGKTHKH VHNGHVFNGS SRSTREKEPV QK HKSKEAT PAKEKHSDHR ADSRREQASA NHPAAAPSTG SSAKGLAATH HHPPLHRSAQ DLRKQVSKVN GVTRMSSLGA GVT SAKKMR EVRPSPSKTV KYTATVTKGA VTYTKAKREL VKDTKPNHHK PSSAVNHTIS GKTESSNAKT RKQVLSLGGA SKST GPAVN GLKVSGRLNP KSCTKEVGGR QLREGLQLRE GLRNSKRRLE EAHQAEKPQS PPKKMKGAAG PAEGPGKKAP AERGL LNGH VKKEVPERSL ERNRPKRATA GKSTPGRQAH GKADSASCEN RSTSQPESVH KPQDSGKAEK GGGKAGWAAM DEIPVL RPS AKEFHDPLIY IESVRAQVEK FGMCRVIPPP DWRPECKLND EMRFVTQIQH IHKLGRRWGP NVQRLACIKK HLKSQGI TM DELPLIGGCE LDLACFFRLI NEMGGMQQVT DLKKWNKLAD MLRIPRTAQD RLAKLQEAYC QYLLSYDSLS PEEHRRLE K EVLMEKEILE KRKGPLEGHT ENDHHKFHPL PRFEPKNGLI HGVAPRNGFR SKLKEVGQAQ LKTGRRRLFA QEKEVVKEE EEDKGVLNDF HKCIYKGRSV SLTTFYRTAR NIMSMCFSKE PAPAEIEQEY WRLVEEKDCH VAVHCGKVDT NTHGSGFPVG KSEPFSRHG WNLTVLPNNT GSILRHLGAV PGVTIPWLNI GMVFSTSCWS RDQNHLPYID YLHTGADCIW YCIPAEEENK L EDVVHTLL QANGTPGLQM LESNVMISPE VLCKEGIKVH RTVQQSGQFV VCFPGSFVSK VCCGYSVSET VHFATTQWTS MG FETAKEM KRRHIAKPFS MEKLLYQIAQ AEAKKENGPT LSTISALLDE LRDTELRQRR QLFEAGLHSS ARYGSHDGSS TVA DGKKKP RKWLQLETSE RRCQICQHLC YLSMVVQENE NVVFCLECAL RHVEKQKSCR GLKLMYRYDE EQIISLVNQI CGKV SGKNG SIENCLSKPT PKRGPRKRAT VDVPPSRLSA SSSSKSASSS S UniProtKB: Protein Jumonji |
-分子 #7: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 7 / コピー数: 8 / 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
濃度 | 0.05 mg/mL | |||||||||||||||
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緩衝液 | pH: 7.9 構成要素:
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凍結 | 凍結剤: ETHANE |
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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 K2 SUMMIT (4k x 4k) 平均電子線量: 47.0 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: OTHER / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |