+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37503 | |||||||||
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Title | Cryo-EM structure of USP16 bound to H2AK119Ub nucleosome | |||||||||
Map data | Main map at a resolution of 3.05 angstrom | |||||||||
Sample |
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Keywords | nucleosome complex / USP16 / H2AK119Ub / NUCLEAR PROTEIN | |||||||||
Function / homology | Function and homology information mitotic nuclear division / histone H2A deubiquitinase activity / monoubiquitinated protein deubiquitination / positive regulation of translational elongation / protein localization to CENP-A containing chromatin / CENP-A containing nucleosome / ribosomal small subunit binding / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity ...mitotic nuclear division / histone H2A deubiquitinase activity / monoubiquitinated protein deubiquitination / positive regulation of translational elongation / protein localization to CENP-A containing chromatin / CENP-A containing nucleosome / ribosomal small subunit binding / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends / positive regulation of ribosome biogenesis / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / telomere organization / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation / Deposition of new CENPA-containing nucleosomes at the centromere / hepoxilin biosynthetic process / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / linoleic acid metabolic process / Meiotic synapsis / Inhibition of DNA recombination at telomere / nucleosomal DNA binding / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / Interleukin-7 signaling / epigenetic regulation of gene expression / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Defective pyroptosis / Meiotic recombination / innate immune response in mucosa / DNA Damage/Telomere Stress Induced Senescence / ubiquitin binding / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Transcriptional regulation of granulopoiesis / HDMs demethylate histones / Formation of the beta-catenin:TCF transactivating complex / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / PKMTs methylate histone lysines / B-WICH complex positively regulates rRNA expression / heterochromatin formation / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / Activation of anterior HOX genes in hindbrain development during early embryogenesis / structural constituent of chromatin / UCH proteinases / nucleosome / antimicrobial humoral immune response mediated by antimicrobial peptide / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / E3 ubiquitin ligases ubiquitinate target proteins / Senescence-Associated Secretory Phenotype (SASP) / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / gene expression / antibacterial humoral response / histone binding / Oxidative Stress Induced Senescence / protein homotetramerization / defense response to Gram-negative bacterium / Estrogen-dependent gene expression / transcription coactivator activity / killing of cells of another organism / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / regulation of cell cycle / Ub-specific processing proteases / defense response to Gram-positive bacterium / cadherin binding / protein heterodimerization activity / Amyloid fiber formation / cell division / negative regulation of cell population proliferation / cysteine-type endopeptidase activity / DNA damage response / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / protein-containing complex Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.05 Å | |||||||||
Authors | Ai HS / He ZZ / Deng ZH / Liu L | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Structural and mechanistic basis for nucleosomal H2AK119 deubiquitination by single-subunit deubiquitinase USP16. Authors: Huasong Ai / Zaozhen He / Zhiheng Deng / Guo-Chao Chu / Qiang Shi / Zebin Tong / Jia-Bin Li / Man Pan / Lei Liu / Abstract: Epigenetic regulators have a crucial effect on gene expression based on their manipulation of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well-established hallmark in ...Epigenetic regulators have a crucial effect on gene expression based on their manipulation of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well-established hallmark in transcription repression, is dynamically regulated by the opposing activities of Polycomb repressive complex 1 (PRC1) and nucleosome deubiquitinases including the primary human USP16 and Polycomb repressive deubiquitinase (PR-DUB) complex. Recently, the catalytic mechanism for the multi-subunit PR-DUB complex has been described, but how the single-subunit USP16 recognizes the H2AK119Ub nucleosome and cleaves the ubiquitin (Ub) remains unknown. Here we report the cryo-EM structure of USP16-H2AK119Ub nucleosome complex, which unveils a fundamentally distinct mode of H2AK119Ub deubiquitination compared to PR-DUB, encompassing the nucleosome recognition pattern independent of the H2A-H2B acidic patch and the conformational heterogeneity in the Ub motif and the histone H2A C-terminal tail. Our work highlights the mechanism diversity of H2AK119Ub deubiquitination and provides a structural framework for understanding the disease-causing mutations of USP16. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37503.map.gz | 4.2 MB | EMDB map data format | |
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Header (meta data) | emd-37503-v30.xml emd-37503.xml | 26.3 KB 26.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_37503_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_37503.png | 162.3 KB | ||
Masks | emd_37503_msk_1.map | 64 MB | Mask map | |
Filedesc metadata | emd-37503.cif.gz | 7 KB | ||
Others | emd_37503_additional_1.map.gz emd_37503_additional_2.map.gz emd_37503_half_map_1.map.gz emd_37503_half_map_2.map.gz | 1.2 MB 4.4 MB 49.7 MB 49.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37503 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37503 | HTTPS FTP |
-Validation report
Summary document | emd_37503_validation.pdf.gz | 725.8 KB | Display | EMDB validaton report |
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Full document | emd_37503_full_validation.pdf.gz | 725.4 KB | Display | |
Data in XML | emd_37503_validation.xml.gz | 15.2 KB | Display | |
Data in CIF | emd_37503_validation.cif.gz | 20.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37503 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37503 | HTTPS FTP |
-Related structure data
Related structure data | 8wg5MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_37503.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Main map at a resolution of 3.05 angstrom | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.074 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_37503_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: USP16-Ub local map at a resolution of 3.05 angstrom
File | emd_37503_additional_1.map | ||||||||||||
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Annotation | USP16-Ub local map at a resolution of 3.05 angstrom | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: USP16-H2AK119Ub complex map at a resolution of 3.35 angstrom
File | emd_37503_additional_2.map | ||||||||||||
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Annotation | USP16-H2AK119Ub complex map at a resolution of 3.35 angstrom | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37503_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_37503_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of USP16 bound to H2AK119Ub nucleosome
Entire | Name: Complex of USP16 bound to H2AK119Ub nucleosome |
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Components |
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-Supramolecule #1: Complex of USP16 bound to H2AK119Ub nucleosome
Supramolecule | Name: Complex of USP16 bound to H2AK119Ub nucleosome / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#8 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Ubiquitin carboxyl-terminal hydrolase 16
Macromolecule | Name: Ubiquitin carboxyl-terminal hydrolase 16 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: ubiquitinyl hydrolase 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 93.70825 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MGKKRTKGKT VPIDDSSETL EPVCRHIRKG LEQGNLKKAL VNVEWNICQD CKTDNKVKDK AEEETEEKPS VWLCLKCGHQ GCGRNSQEQ HALKHYLTPR SEPHCLVLSL DNWSVWCYVC DNEVQYCSSN QLGQVVDYVR KQASITTPKP AEKDNGNIEL E NKKLEKES ...String: MGKKRTKGKT VPIDDSSETL EPVCRHIRKG LEQGNLKKAL VNVEWNICQD CKTDNKVKDK AEEETEEKPS VWLCLKCGHQ GCGRNSQEQ HALKHYLTPR SEPHCLVLSL DNWSVWCYVC DNEVQYCSSN QLGQVVDYVR KQASITTPKP AEKDNGNIEL E NKKLEKES KNEQEREKKE NMAKENPPMN SPCQITVKGL SNLGNTCFFN AVMQNLSQTP VLRELLKEVK MSGTIVKIEP PD LALTEPL EINLEPPGPL TLAMSQFLNE MQETKKGVVT PKELFSQVCK KAVRFKGYQQ QDSQELLRYL LDGMRAEEHQ RVS KGILKA FGNSTEKLDE ELKNKVKDYE KKKSMPSFVD RIFGGELTSM IMCDQCRTVS LVHESFLDLS LPVLDDQSGK KSVN DKNLK KTVEDEDQDS EEEKDNDSYI KERSDIPSGT SKHLQKKAKK QAKKQAKNQR RQQKIQGKVL HLNDICTIDH PEDSE YEAE MSLQGEVNIK SNHISQEGVM HKEYCVNQKD LNGQAKMIES VTDNQKSTEE VDMKNINMDN DLEVLTSSPT RNLNGA YLT EGSNGEVDIS NGFKNLNLNA ALHPDEINIE ILNDSHTPGT KVYEVVNEDP ETAFCTLANR EVFNTDECSI QHCLYQF TR NEKLRDANKL LCEVCTRRQC NGPKANIKGE RKHVYTNAKK QMLISLAPPV LTLHLKRFQQ AGFNLRKVNK HIKFPEIL D LAPFCTLKCK NVAEENTRVL YSLYGVVEHS GTMRSGHYTA YAKARTANSH LSNLVLHGDI PQDFEMESKG QWFHISDTH VQAVPTTKVL NSQAYLLFYE RIL UniProtKB: Ubiquitin carboxyl-terminal hydrolase 16 |
-Macromolecule #2: Histone H3.1
Macromolecule | Name: Histone H3.1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.562577 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: KPHRYRPGTV ALREIRRYQK STELLIRKLP FQRLVREIAQ DFKTDLRFQS SAVMALQEAC EAYLVGLFED TNLCAIHAKR VTIMPKDIQ LARRIRGER UniProtKB: Histone H3.1 |
-Macromolecule #3: Histone H4
Macromolecule | Name: Histone H4 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 9.010534 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: RDNIQGITKP AIRRLARRGG VKRISGLIYE ETRGVLKVFL ENVIRDAVTY TEHAKRKTVT AMDVVYALKR QGRTLYGFG UniProtKB: Arachidonate 15-lipoxygenase |
-Macromolecule #4: Histone H2A type 1-B/E
Macromolecule | Name: Histone H2A type 1-B/E / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.141195 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: ARAKAKTRSS RAGLQFPVGR VHRLLRKGNY SERVGAGAPV YLAAVLEYLT AEILELAGNA ARDNKKTRII PRHLQLAIRN DEELNKLLG RVTIAQGGVL PNIQAVLLPK CT UniProtKB: Histone H2A type 1-B/E |
-Macromolecule #5: Histone H2B type 1-K
Macromolecule | Name: Histone H2B type 1-K / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 10.477994 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: RSRKESYSVY VYKVLKQVHP DTGISSKAMG IMNSFVNDIF ERIAGEASRL AHYNKRSTIT SREIQTAVRL LLPGELAKHA VSEGTKAVT KYTSA UniProtKB: Histone H2B type 1-K |
-Macromolecule #8: Ubiquitin B
Macromolecule | Name: Ubiquitin B / type: protein_or_peptide / ID: 8 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 8.622922 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGC UniProtKB: Ubiquitin B |
-Macromolecule #6: DNA (147-MER)
Macromolecule | Name: DNA (147-MER) / type: dna / ID: 6 / Number of copies: 1 / Classification: DNA |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 45.604047 KDa |
Sequence | String: (DA)(DC)(DA)(DG)(DG)(DA)(DT)(DG)(DT)(DA) (DT)(DA)(DT)(DA)(DT)(DC)(DT)(DG)(DA)(DC) (DA)(DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG) (DG)(DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG) (DA) (DG)(DT)(DA)(DA)(DT)(DC) ...String: (DA)(DC)(DA)(DG)(DG)(DA)(DT)(DG)(DT)(DA) (DT)(DA)(DT)(DA)(DT)(DC)(DT)(DG)(DA)(DC) (DA)(DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG) (DG)(DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG) (DA) (DG)(DT)(DA)(DA)(DT)(DC)(DC)(DC) (DC)(DT)(DT)(DG)(DG)(DC)(DG)(DG)(DT)(DT) (DA)(DA) (DA)(DA)(DC)(DG)(DC)(DG)(DG) (DG)(DG)(DG)(DA)(DC)(DA)(DG)(DC)(DG)(DC) (DG)(DT)(DA) (DC)(DG)(DT)(DG)(DC)(DG) (DT)(DT)(DT)(DA)(DA)(DG)(DC)(DG)(DG)(DT) (DG)(DC)(DT)(DA) (DG)(DA)(DG)(DC)(DT) (DG)(DT)(DC)(DT)(DA)(DC)(DG)(DA)(DC)(DC) (DA)(DA)(DT)(DT)(DG) (DA)(DG)(DC)(DG) (DG)(DC)(DC)(DT)(DC)(DG)(DG)(DC)(DA)(DC) (DC)(DG)(DG)(DG)(DA)(DT) (DT)(DC)(DT) (DC)(DC)(DA)(DG) |
-Macromolecule #7: DNA (147-MER)
Macromolecule | Name: DNA (147-MER) / type: dna / ID: 7 / Number of copies: 1 / Classification: DNA |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 45.145754 KDa |
Sequence | String: (DC)(DT)(DG)(DG)(DA)(DG)(DA)(DA)(DT)(DC) (DC)(DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA) (DG)(DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA) (DA)(DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA) (DG) (DA)(DC)(DA)(DG)(DC)(DT) ...String: (DC)(DT)(DG)(DG)(DA)(DG)(DA)(DA)(DT)(DC) (DC)(DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA) (DG)(DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA) (DA)(DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA) (DG) (DA)(DC)(DA)(DG)(DC)(DT)(DC)(DT) (DA)(DG)(DC)(DA)(DC)(DC)(DG)(DC)(DT)(DT) (DA)(DA) (DA)(DC)(DG)(DC)(DA)(DC)(DG) (DT)(DA)(DC)(DG)(DC)(DG)(DC)(DT)(DG)(DT) (DC)(DC)(DC) (DC)(DC)(DG)(DC)(DG)(DT) (DT)(DT)(DT)(DA)(DA)(DC)(DC)(DG)(DC)(DC) (DA)(DA)(DG)(DG) (DG)(DG)(DA)(DT)(DT) (DA)(DC)(DT)(DC)(DC)(DC)(DT)(DA)(DG)(DT) (DC)(DT)(DC)(DC)(DA) (DG)(DG)(DC)(DA) (DC)(DG)(DT)(DG)(DT)(DC)(DA)(DG)(DA)(DT) (DA)(DT)(DA)(DT)(DA)(DC) (DA)(DT)(DC) (DC)(DT)(DG)(DT) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.3 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |