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Yorodumi- PDB-7bx7: Cryo-EM structure of amyloid fibril formed by hnRNPA1 low complex... -
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-Basic information
Entry | Database: PDB / ID: 7bx7 | ||||||
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Title | Cryo-EM structure of amyloid fibril formed by hnRNPA1 low complexity domain | ||||||
Components | Heterogeneous nuclear ribonucleoprotein A1 | ||||||
Keywords | PROTEIN FIBRIL / amyloid fibril | ||||||
Function / homology | Function and homology information cellular response to sodium arsenite / SARS-CoV-1-host interactions / import into nucleus / telomeric repeat-containing RNA binding / G-rich strand telomeric DNA binding / pre-mRNA binding / nuclear export / RNA export from nucleus / miRNA binding / FGFR2 alternative splicing ...cellular response to sodium arsenite / SARS-CoV-1-host interactions / import into nucleus / telomeric repeat-containing RNA binding / G-rich strand telomeric DNA binding / pre-mRNA binding / nuclear export / RNA export from nucleus / miRNA binding / FGFR2 alternative splicing / regulation of alternative mRNA splicing, via spliceosome / intracellular non-membrane-bounded organelle / SARS-CoV-1 modulates host translation machinery / regulation of RNA splicing / negative regulation of telomere maintenance via telomerase / Processing of Capped Intron-Containing Pre-mRNA / mRNA transport / cellular response to glucose starvation / localization / positive regulation of telomere maintenance via telomerase / catalytic step 2 spliceosome / molecular condensate scaffold activity / mRNA Splicing - Major Pathway / mRNA 3'-UTR binding / spliceosomal complex / mRNA splicing, via spliceosome / single-stranded DNA binding / amyloid fibril formation / single-stranded RNA binding / ribonucleoprotein complex / protein domain specific binding / DNA binding / RNA binding / extracellular exosome / nucleoplasm / membrane / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
Authors | Sun, Y.P. / Zhao, K. / Liu, C. / Li, D. | ||||||
Citation | Journal: Nat Commun / Year: 2020 Title: The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure. Authors: Yunpeng Sun / Kun Zhao / Wencheng Xia / Guoqin Feng / Jinge Gu / Yeyang Ma / Xinrui Gui / Xia Zhang / Yanshan Fang / Bo Sun / Renxiao Wang / Cong Liu / Dan Li / Abstract: Human heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation ...Human heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-β2 (Kapβ2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapβ2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminates structural understandings of the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapβ2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7bx7.cif.gz | 56 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7bx7.ent.gz | 39.2 KB | Display | PDB format |
PDBx/mmJSON format | 7bx7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bx/7bx7 ftp://data.pdbj.org/pub/pdb/validation_reports/bx/7bx7 | HTTPS FTP |
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-Related structure data
Related structure data | 30235MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 13082.421 Da / Num. of mol.: 6 / Fragment: low complexity domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HNRNPA1, HNRPA1 / Production host: Escherichia coli (E. coli) / References: UniProt: P09651 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Amyloid fibril formed by hnRNPA1 low complexity domain Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 59 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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Helical symmerty | Angular rotation/subunit: 179.054 ° / Axial rise/subunit: 2.371 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 69037 / Symmetry type: HELICAL |