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-Structure paper
Title | Cryo-EM Structure of the Full-length hnRNPA1 Amyloid Fibril. |
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Journal, issue, pages | J Mol Biol, Vol. 435, Issue 18, Page 168211, Year 2023 |
Publish date | Sep 15, 2023 |
Authors | Kartikay Sharma / Sambhasan Banerjee / Dilan Savran / Cedric Rajes / Sebastian Wiese / Amandeep Girdhar / Nadine Schwierz / Christopher Lee / James Shorter / Matthias Schmidt / Lin Guo / Marcus Fändrich / |
PubMed Abstract | Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a multifunctional RNA-binding protein that is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis and multisystem ...Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a multifunctional RNA-binding protein that is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis and multisystem proteinopathy. In this study, we have used cryo-electron microscopy to investigate the three-dimensional structure of amyloid fibrils from full-length hnRNPA1 protein. We find that the fibril core is formed by a 45-residue segment of the prion-like low-complexity domain of the protein, whereas the remaining parts of the protein (275 residues) form a fuzzy coat around the fibril core. The fibril consists of two fibril protein stacks that are arranged into a pseudo-2 screw symmetry. The ordered core harbors several of the positions that are known to be affected by disease-associated mutations, but does not encompass the most aggregation-prone segments of the protein. These data indicate that the structures of amyloid fibrils from full-length proteins may be more complex than anticipated by current theories on protein misfolding. |
External links | J Mol Biol / PubMed:37481159 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 3.32 Å |
Structure data | EMDB-14739, PDB-7zj2: |
Source |
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Keywords | NUCLEAR PROTEIN / Amyloidosis / Misfolding disease / Inflammation / Prion / Protein fibril |