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- EMDB-30235: Cryo-EM structure of amyloid fibril formed by hnRNPA1 low complex... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30235 | |||||||||
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Title | Cryo-EM structure of amyloid fibril formed by hnRNPA1 low complexity domain | |||||||||
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Function / homology | ![]() cellular response to sodium arsenite / SARS-CoV-1-host interactions / import into nucleus / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | helical reconstruction / ![]() | |||||||||
![]() | Sun YP / Zhao K | |||||||||
![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 4.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 9 KB 9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.2 KB | Display | ![]() |
Images | ![]() | 71.4 KB | ||
Filedesc metadata | ![]() | 4.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7bx7MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Amyloid fibril formed by hnRNPA1 low complexity domain
Entire | Name: Amyloid fibril formed by hnRNPA1 low complexity domain |
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Components |
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-Supramolecule #1: Amyloid fibril formed by hnRNPA1 low complexity domain
Supramolecule | Name: Amyloid fibril formed by hnRNPA1 low complexity domain type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Heterogeneous nuclear ribonucleoprotein A1
Macromolecule | Name: Heterogeneous nuclear ribonucleoprotein A1 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 13.082421 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MASASSSQRG RSGSGNFGGG RGGGFGGNDN FGRGGNFSGR GGFGGSRGGG GYGGSGDGYN GFGNDGSNFG GGGSYNDFGN YNNQSSNFG PMKGGNFGGR SSGPYGGGGQ YFAKPRNQGG YGGSSSSSSY GSGRRF UniProtKB: Heterogeneous nuclear ribonucleoprotein A1 |
-Experimental details
-Structure determination
Method | ![]() |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 5 |
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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: 59.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |