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Open data
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Basic information
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Title | SLFN11 E209A monomer | |||||||||
![]() | sharpened map | |||||||||
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Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Metzner FJ / Kugler M / Wenzl SJ / Lammens K | |||||||||
Funding support | ![]()
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![]() | ![]() 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. | |||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.1 KB 14.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.5 KB | Display | ![]() |
Images | ![]() | 55.2 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Others | ![]() ![]() | 59.3 MB 59.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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
-Mask #1
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Density Histograms |
-Half map: half map A
File | emd_14693_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
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-Half map: half map B
File | emd_14693_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
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Density Histograms |
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Sample components
-Entire : SLFN11 E209A monomer
Entire | Name: SLFN11 E209A monomer |
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Components |
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-Supramolecule #1: SLFN11 E209A monomer
Supramolecule | Name: SLFN11 E209A monomer / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: SLFN11 E209A
Macromolecule | Name: SLFN11 E209A / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
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 EILPFPASQL 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 | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 9 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 43.58 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |