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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | Retron-Kva2 Complex Composite | |||||||||
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Sample |
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Keywords | Retron / Reverse transcriptase / Bacterial immune system / Abi / Ribonuclease / IMMUNE SYSTEM | |||||||||
| Biological species | Klebsiella variicola (bacteria) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Hibshman GN | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2026Title: Higher-order assembly of a type IX retron enables exploitation for designer antimicrobials. Authors: Grace N Hibshman / Linhan Wang / Nicole MacRae / Karen Zhang / Alfredo Florez / Seth L Shipman / Eva Nogales / ![]() Abstract: Bacterial defense systems provide a rich reservoir for biotechnological innovation. Retrons are tripartite abortive infection systems that detect phage invasion using reverse-transcribed DNA (msDNA), ...Bacterial defense systems provide a rich reservoir for biotechnological innovation. Retrons are tripartite abortive infection systems that detect phage invasion using reverse-transcribed DNA (msDNA), but how they structurally couple threat detection to effector activation remains poorly understood. Here, we determine the cryo-EM structure and activation mechanism of retron-Kva2, a type IX retron from the human pathogen . We reveal that retron-Kva2 assembles into an asymmetric, higher-order ribonucleoprotein complex that sequesters a toxic dimeric HEPN RNase at its core. We identify a natural phage trigger as the phage T5 protein D5, which activates the retron through structural mimicry. Mirroring the retron-Kva2 winged-helix protein, the helix-turn-helix fold of D5 binds the msDNA sensor, driving conformational remodeling that unleashes HEPN-mediated tRNA cleavage and growth arrest. Because retron-Kva2 surveils a structural fold via msDNA binding, rather than a primary sequence, this recognition mechanism provides a broadly exploitable pathway for programmable activation. Harnessing this structure-based logic, we computationally designed synthetic triggers that activate retron-Kva2-mediated bacterial growth arrest . Our findings reveal the architectural basis of type IX retron immunity and establish a structure-guided paradigm for repurposing bacterial defense systems into precision-honed antimicrobial therapeutics. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_77585.map.gz | 134.9 MB | EMDB map data format | |
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| Header (meta data) | emd-77585-v30.xml emd-77585.xml | 17.2 KB 17.2 KB | Display Display | EMDB header |
| Images | emd_77585.png | 79 KB | ||
| Filedesc metadata | emd-77585.cif.gz | 6.4 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-77585 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-77585 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_77585.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.14 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Higher order assembly of retron Kva2
| Entire | Name: Higher order assembly of retron Kva2 |
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| Components |
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-Supramolecule #1: Higher order assembly of retron Kva2
| Supramolecule | Name: Higher order assembly of retron Kva2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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| Source (natural) | Organism: Klebsiella variicola (bacteria) |
| Molecular weight | Theoretical: 397 KDa |
-Macromolecule #1: Retron-Kva2 Reverse Transcriptase
| Macromolecule | Name: Retron-Kva2 Reverse Transcriptase / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Klebsiella variicola (bacteria) |
| Molecular weight | Theoretical: 37.382836 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MKTPLPLLFS YNDAQQFLGA LSPEVRDVYS PEINRLFDRG LPPVVSWSVL SVAIGVSPHF INSIIKNKDK YYRIFPIAKG KGKKVRIIE SPRVGLKIIQ SWLAHHLATN DNIPVSDSAY AFIPGKNGIY EAAFRHCNAK WVLSIDLRDF FHSIDFDRVI N GLRNTGYT ...String: MKTPLPLLFS YNDAQQFLGA LSPEVRDVYS PEINRLFDRG LPPVVSWSVL SVAIGVSPHF INSIIKNKDK YYRIFPIAKG KGKKVRIIE SPRVGLKIIQ SWLAHHLATN DNIPVSDSAY AFIPGKNGIY EAAFRHCNAK WVLSIDLRDF FHSIDFDRVI N GLRNTGYT FEQSGKIAAI VTYKNRLPQG APSSPVLSNI VFKDTDDKIN DIIADKKIIY TRYADDLTFS SDDLSIDVEN LK QNIINLL ENENWTIATE KLKISKIPNR LKVHGFLVHD VKPRLTKGYR NKLRTYEHLL RNGKIIESDL NRIRGHVNYG KHI DKLNDE N |
-Macromolecule #2: Retron-Kva2 WH
| Macromolecule | Name: Retron-Kva2 WH / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Klebsiella variicola (bacteria) |
| Molecular weight | Theoretical: 28.262975 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MYSKEMLEYI LGKYPIISVR EVNDFSETIL LDIPINRLSP AAKNGFITKR QVSNITKKIE SELSVKVLVS YSTSQSKLDI EAGLKALAK ANFKGKKIID LDVSFEDVKN ASVYIFSMNM SDEDKEKWGL LAGDYFSSLN IKLNALMYEQ KNNPEPTLMI M LRTMKILY ...String: MYSKEMLEYI LGKYPIISVR EVNDFSETIL LDIPINRLSP AAKNGFITKR QVSNITKKIE SELSVKVLVS YSTSQSKLDI EAGLKALAK ANFKGKKIID LDVSFEDVKN ASVYIFSMNM SDEDKEKWGL LAGDYFSSLN IKLNALMYEQ KNNPEPTLMI M LRTMKILY PCDLPTMKKA LEDKEYHIES SDWLNKKLDS LRKKNLIIRD REGTYRMTYL GLELVPVTRS KQSSDVDRIL YL AKKHL |
-Macromolecule #5: Retron-Kva2 HEPN
| Macromolecule | Name: Retron-Kva2 HEPN / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: Klebsiella variicola (bacteria) |
| Molecular weight | Theoretical: 19.43568 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MTALYEVAEH LTKQAKASHR KGAQTIVLAD AFARSAFNRY YYACFLCIRT FVSSIEAKWS NVAHLDVPNL LRNNVKQKID AELKKGEKI GILTPGGYQS KKSMVLTSLE IMASTMSLAY IVRGIVDYEP EIKIMFNEGA FSINATSVAE AKGWLMTIKT E EAKIKRIL QEVGIV |
-Macromolecule #3: Retron-Kva2 msdDNA
| Macromolecule | Name: Retron-Kva2 msdDNA / type: dna / ID: 3 / Number of copies: 4 / Classification: DNA |
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| Source (natural) | Organism: Klebsiella variicola (bacteria) |
| Molecular weight | Theoretical: 25.283123 KDa |
| Sequence | String: (DG)(DT)(DT)(DG)(DA)(DT)(DG)(DA)(DC)(DG) (DC)(DC)(DT)(DG)(DT)(DG)(DA)(DA)(DG)(DC) (DA)(DG)(DC)(DA)(DG)(DG)(DC)(DG)(DT) (DT)(DT)(DC)(DG)(DA)(DA)(DG)(DG)(DA)(DG) (DC) (DG)(DC)(DC)(DT)(DG)(DC) ...String: (DG)(DT)(DT)(DG)(DA)(DT)(DG)(DA)(DC)(DG) (DC)(DC)(DT)(DG)(DT)(DG)(DA)(DA)(DG)(DC) (DA)(DG)(DC)(DA)(DG)(DG)(DC)(DG)(DT) (DT)(DT)(DC)(DG)(DA)(DA)(DG)(DG)(DA)(DG) (DC) (DG)(DC)(DC)(DT)(DG)(DC)(DT)(DG) (DC)(DT)(DT)(DC)(DA)(DC)(DA)(DG)(DG)(DC) (DG)(DC) (DA)(DC)(DA)(DT)(DT)(DC)(DT) (DG)(DT)(DA)(DC)(DG)(DC)(DG)(DA)(DC)(DC) (DT)(DT)(DC) (DA)(DC) GENBANK: GENBANK: CP017284.1 |
-Macromolecule #4: Retron-Kva2 msrRNA
| Macromolecule | Name: Retron-Kva2 msrRNA / type: rna / ID: 4 / Number of copies: 3 |
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| Source (natural) | Organism: Klebsiella variicola (bacteria) |
| Molecular weight | Theoretical: 55.65598 KDa |
| Sequence | String: GGUAGUGGCG UUCACGAGGG UGUGUAUCAU ACCCAUUUGU GAAGGUCGCG UACAGAAUGU GCGCCUGUGA AGCAGCAGGC GCUCCUUCG AAACGCCUGC UGCUUCACAG GCGUCAUCAA CGAAAGCCUC AUCAGCUUUG CUUAAGGACU GACCUGGAUG A AAACGCCA CUACC GENBANK: GENBANK: CP017284.1 |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TALOS ARCTICA |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Keywords
Klebsiella variicola (bacteria)
Authors
United States, 1 items
Citation




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Processing
FIELD EMISSION GUN
