+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14695 | |||||||||
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Title | SLFN11 dimer bound to tRNA | |||||||||
Map data | unsharpened map | |||||||||
Sample |
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Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Metzner FJ / Kugler M / Wenzl SJ / Lammens K | |||||||||
Funding support | Germany, European Union, 2 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Mechanistic understanding of human SLFN11. Authors: Felix J Metzner / Simon J Wenzl / Michael Kugler / Stefan Krebs / Karl-Peter Hopfner / Katja Lammens / Abstract: Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to ...Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to replication stress and inhibits replication of certain viruses such as the human immunodeficiency virus 1 (HIV-1) by modulating the tRNA pool. SLFN11 has been identified as a predictive biomarker in cancer, as its expression correlates with a beneficial response to DNA damage inducing anticancer drugs. However, the mechanism and interdependence of these two functions are largely unknown. Here, we present cryo-electron microscopy (cryo-EM) structures of human SLFN11 in its dimeric apoenzyme state, bound to tRNA and in complex with single-strand DNA. Full-length SLFN11 neither hydrolyses nor binds ATP and the helicase domain appears in an autoinhibited state. Together with biochemical and structure guided mutagenesis studies, our data give detailed insights into the mechanism of endoribonuclease activity as well as suggestions on how SLFN11 may block stressed replication forks. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14695.map.gz | 62.8 MB | EMDB map data format | |
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Header (meta data) | emd-14695-v30.xml emd-14695.xml | 13.9 KB 13.9 KB | Display Display | EMDB header |
Images | emd_14695.png | 66.4 KB | ||
Others | emd_14695_half_map_1.map.gz emd_14695_half_map_2.map.gz | 116.1 MB 116.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14695 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14695 | HTTPS FTP |
-Validation report
Summary document | emd_14695_validation.pdf.gz | 699 KB | Display | EMDB validaton report |
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Full document | emd_14695_full_validation.pdf.gz | 698.6 KB | Display | |
Data in XML | emd_14695_validation.xml.gz | 13.8 KB | Display | |
Data in CIF | emd_14695_validation.cif.gz | 16.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14695 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14695 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_14695.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | unsharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.046 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half map A
File | emd_14695_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_14695_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SLFN11 dimer bound to tRNA
Entire | Name: SLFN11 dimer bound to tRNA |
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Components |
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-Supramolecule #1: SLFN11 dimer bound to tRNA
Supramolecule | Name: SLFN11 dimer bound to tRNA / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
-Macromolecule #1: SLFN11
Macromolecule | Name: SLFN11 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MADYKDDDDK GTDYKDDDDK LEVLFQGPME ANQCPLVVEP SYPDLVINVG EVTLGEENRK KLQKIQRDQE KERVMRAACA LLNSGGGVIR MAKKVEHPVE MGLDLEQSLR ELIQSSDLQA FFETKQQGRC FYIFVKSWSS GPFPEDRSVK PRLCSLSSSL YRRSETSVRS ...String: MADYKDDDDK GTDYKDDDDK LEVLFQGPME ANQCPLVVEP SYPDLVINVG EVTLGEENRK KLQKIQRDQE KERVMRAACA LLNSGGGVIR MAKKVEHPVE MGLDLEQSLR ELIQSSDLQA FFETKQQGRC FYIFVKSWSS GPFPEDRSVK PRLCSLSSSL YRRSETSVRS MDSREAFCFL KTKRKPKILE EGPFHKIHKG VYQELPNSDP ADPNSDPADL IFQKDYLEYG EILPFPESQL VEFKQFSTKH FQEYVKRTIP EYVPAFANTG GGYLFIGVDD KSREVLGCAK ENVDPDSLRR KIEQAIYKLP CVHFCQPQRP ITFTLKIVNV LKRGELYGYA CMIRVNPFCC AVFSEAPNSW IVEDKYVCSL TTEKWVGMMT DTDPDLLQLS EDFECQLSLS SGPPLSRPVY SKKGLEHKKE LQQLLFSVPP GYLRYTPESL WRDLISEHRG LEELINKQMQ PFFRGILIFS RSWAVDLNLQ EKPGVICDAL LIAQNSTPIL YTILREQDAE GQDYCTRTAF TLKQKLVNMG GYTGKVCVRA KVLCLSPESS AEALEAAVSP MDYPASYSLA GTQHMEALLQ SLVIVLLGFR SLLSDQLGCE VLNLLTAQQY EIFSRSLRKN RELFVHGLPG SGKTIMAMKI MEKIRNVFHC EAHRILYVCE NQPLRNFISD RNICRAETRK TFLRENFEHI QHIVIDEAQN FRTEDGDWYG KAKSITRRAK GGPGILWIFL DYFQTSHLDC SGLPPLSDQY PREELTRIVR NADPIAKYLQ KEMQVIRSNP SFNIPTGCLE VFPEAEWSQG VQGTLRIKKY LTVEQIMTCV ADTCRRFFDR GYSPKDVAVL VSTAKEVEHY KYELLKAMRK KRVVQLSDAC DMLGDHIVLD SVRRFSGLER SIVFGIHPRT ADPAILPNVL ICLASRAKQH LYIFPWGGH |
-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 K2 SUMMIT (4k x 4k) / Average electron dose: 49.65 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: 2.9 µm / Nominal defocus min: 1.1 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 96514 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |