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- EMDB-67441: Structure of Human Aspartate--tRNA ligase 3-154 with linker and F... -

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Basic information

Entry
Database: EMDB / ID: EMD-67441
TitleStructure of Human Aspartate--tRNA ligase 3-154 with linker and FC : ATYR0101
Map data
Sample
  • Complex: Human Aspartate--tRNA ligase 3-154: -Linker-Fcv14
    • Protein or peptide: Aspartate--tRNA ligase, cytoplasmic,linker+FC
KeywordsApoptosis / Fibrosis / t-RNA synthase / Myofibroblast
Function / homology
Function and homology information


aminoacylase activity / aspartate-tRNA ligase / aspartate-tRNA ligase activity / aspartyl-tRNA aminoacylation / Selenoamino acid metabolism / Cytosolic tRNA aminoacylation / aminoacyl-tRNA synthetase multienzyme complex / tRNA aminoacylation for protein translation / Transcriptional and post-translational regulation of MITF-M expression and activity / protein-containing complex assembly ...aminoacylase activity / aspartate-tRNA ligase / aspartate-tRNA ligase activity / aspartyl-tRNA aminoacylation / Selenoamino acid metabolism / Cytosolic tRNA aminoacylation / aminoacyl-tRNA synthetase multienzyme complex / tRNA aminoacylation for protein translation / Transcriptional and post-translational regulation of MITF-M expression and activity / protein-containing complex assembly / translation / synapse / RNA binding / extracellular exosome / ATP binding / membrane / cytosol / cytoplasm
Similarity search - Function
Aspartate-tRNA synthetase, type 2 / Aspartyl/Asparaginyl-tRNA synthetase, class IIb / Aminoacyl-tRNA synthetase, class II (D/K/N) / tRNA synthetases class II (D, K and N) / OB-fold nucleic acid binding domain, AA-tRNA synthetase-type / OB-fold nucleic acid binding domain / Aminoacyl-tRNA synthetase, class II / Aminoacyl-transfer RNA synthetases class-II family profile. / Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL) / Nucleic acid-binding, OB-fold
Similarity search - Domain/homology
Aspartate--tRNA ligase, cytoplasmic
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.96 Å
AuthorsNangle L / Tian H / Fung CP
Funding support Hong Kong, 1 items
OrganizationGrant numberCountry
Other government Hong Kong
CitationJournal: J Biol Chem / Year: 2026
Title: Natural Asp-tRNA Synthetase Fragment Targets Myofibroblasts to Abrogate Tissue Fibrosis.
Authors: Ryan A Adams / Ying-Ting Wang / Alison G Barber / Kristina Hamel / Andrew Imfeld / Luke Burman / Kaitlyn Rauch / Yeeting E Chong / Angelica Villanueva / Lauren Guy / Wayne Liu / Crystal ...Authors: Ryan A Adams / Ying-Ting Wang / Alison G Barber / Kristina Hamel / Andrew Imfeld / Luke Burman / Kaitlyn Rauch / Yeeting E Chong / Angelica Villanueva / Lauren Guy / Wayne Liu / Crystal Manzo / Sofia Klopp-Savino / Clara Polizzi / Jasmine Stamps / Max Pastenes / Honglei Tian / Chun Po Fung / Yingyi Zhang / Kwok Wa Hugo Ho / Bruno Sangiorgi / Blythe Dillingham / Tarsis F Brust / Kyle P Chiang / Zhenguo Wu / Zhiwen Xu / Christoph Burkart / Leslie A Nangle /
Abstract: Fibrosis remains a major global health challenge with limited therapies that only slow disease progression. While the aminoacyl-tRNA synthetase (aaRS) family is known to utilize evolutionarily ...Fibrosis remains a major global health challenge with limited therapies that only slow disease progression. While the aminoacyl-tRNA synthetase (aaRS) family is known to utilize evolutionarily appended domains as extracellular signaling molecules, their role in regulating the homeostasis of the fibrotic process is poorly defined. We identify a natural proteolytic fragment of aspartyl-tRNA synthetase (DARS), termed DARS-N1, that selectively triggers apoptosis in myofibroblasts by targeting latent-transforming growth factor beta binding protein 1 (LTBP-1) on the extracellular matrix (ECM). This active N-terminal fragment of DARS reduces focal adhesion kinase (FAK) activation in undifferentiated fibroblasts and myofibroblasts, while only myofibroblasts exhibit inadequate cell-matrix attachment leading to loss of anchorage-dependent survival and promotion of apoptosis. We utilized ATYR0101, a therapeutic form of DARS-N1 engineered for extended serum exposure, to demonstrate anti-fibrotic activity in lung (bleomycin). Spatial transcriptomics analysis showed that ATYR0101 activates a restorative program promoting the return to a healthy state. These findings highlight ATYR0101's potential as a transformative therapy for disrupting the process of chronic tissue fibrosis.
History
DepositionDec 4, 2025-
Header (metadata) releaseOct 14, 2026-
Map releaseOct 14, 2026-
UpdateOct 14, 2026-
Current statusOct 14, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_67441.png

Downloads & links

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Map

FileDownload / File: emd_67441.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
1.06 Å/pix.
x 200 pix.
= 212. Å		1.06 Å/pix.
x 200 pix.
= 212. Å		1.06 Å/pix.
x 200 pix.
= 212. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.045
Minimum - Maximum-0.56460136 - 0.59500104
Average (Standard dev.)-0.0003839397 (±0.017707482)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 211.99998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_67441_half_map_1.map
Projections & Slices
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Half map: #1

Fileemd_67441_half_map_2.map
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Sample components

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Entire : Human Aspartate--tRNA ligase 3-154: -Linker-Fcv14

EntireName: Human Aspartate--tRNA ligase 3-154: -Linker-Fcv14
Components
  • Complex: Human Aspartate--tRNA ligase 3-154: -Linker-Fcv14
    • Protein or peptide: Aspartate--tRNA ligase, cytoplasmic,linker+FC

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Supramolecule #1: Human Aspartate--tRNA ligase 3-154: -Linker-Fcv14

SupramoleculeName: Human Aspartate--tRNA ligase 3-154: -Linker-Fcv14 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Details: Recombinant protein of N-terminal of Human Aspartate tRNA ligase and IgG FC
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Aspartate--tRNA ligase, cytoplasmic,linker+FC

MacromoleculeName: Aspartate--tRNA ligase, cytoplasmic,linker+FC / type: protein_or_peptide / ID: 1
Details: N-terminal portion is flexible random loop and not visible in structure,N-terminal portion is flexible random loop and not visible in structure
Number of copies: 2 / Enantiomer: LEVO / EC number: aspartate-tRNA ligase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 45.527676 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SASASRKSQE KPREIMDAAE DYAKERYGIS SMIQSQEKPD RVLVRVRDLT IQKADEVVWV RARVHTSRAK GKQCFLVLCQ QQFCVQALV AVGDHASKQM VKFAANINKE SIVDVEGVVR KVNQKIGSST QQDVELHVQK IYVISLAEPR LPLAPAPAPA P APAPAPAP ...String:
SASASRKSQE KPREIMDAAE DYAKERYGIS SMIQSQEKPD RVLVRVRDLT IQKADEVVWV RARVHTSRAK GKQCFLVLCQ QQFCVQALV AVGDHASKQM VKFAANINKE SIVDVEGVVR KVNQKIGSST QQDVELHVQK IYVISLAEPR LPLAPAPAPA P APAPAPAP APAPAPAPAP APAPAESKYG PPCPPCPAPE FEGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSQEDPEV QF NWYVDGV EVHNAKTKPR EEQFNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKGLPSSI EKTISKAKGQ PREPQVYTLP PSQ EEMTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSRLT VDKSRWQEGN VFSCSVMHEA LHNH YTQKS LSLSLGK

UniProtKB: Aspartate--tRNA ligase, cytoplasmic

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1 mg/mL
BufferpH: 7.4 / Details: 1x PBS 7.4
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 291.15 K / Instrument: FEI VITROBOT MARK IV
Details: To prepare cryo-grids, 3 ul samples were applied to glow discharged Quantifoil Cu grids (R1.2/1.3), which were subsequently blotted with filter paper (Ted Pella) for 3 seconds at 18oC and ...Details: To prepare cryo-grids, 3 ul samples were applied to glow discharged Quantifoil Cu grids (R1.2/1.3), which were subsequently blotted with filter paper (Ted Pella) for 3 seconds at 18oC and 100% humidity. The grids were immediately plunge frozen in liquid ethane using a FEI Vitrobot IV (ThermoFisher).
DetailsThis sample is purified from Expi293F expression

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Number real images: 1414 / Average electron dose: 50.0 e/Å2
Details: A total of 1,508 movies were acquired and imported into Cryo-SPARC using the following parameters: Raw pixel size 1.06 A, Accelerating Voltage 300 kV, Spherical Aberration 2.7 mm, and Total ...Details: A total of 1,508 movies were acquired and imported into Cryo-SPARC using the following parameters: Raw pixel size 1.06 A, Accelerating Voltage 300 kV, Spherical Aberration 2.7 mm, and Total exposure dose 50 e/A^2. Motion correction and CTF estimation were performed using Full-frame Motion Correction and Patch CTF. After that, 1,414 micrographs were selected from the 1,508 micrographs based on average intensity
Electron beamAcceleration voltage: 300 kV / Electron source: OTHER
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionDetails: After Inspect Particle Picks (NCC score > 0.670, 10 < local power score < 59) and Extract From Micrographs (Extraction box size 200 pix), a total of 2,771,298 particles were extracted
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.96 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.7.0) / Number images used: 142250
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model / Details: Intial model of st
DetailsInitial local fitting was done using Chimera X, followed by manual fitting using Coot. Finally it was refined using Phenix real space refinement
RefinementSpace: REAL / Protocol: AB INITIO MODEL
Output model

PDB-21aa:
Structure of Human Aspartate--tRNA ligase 3-154 with linker and FC : ATYR0101

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