7ZJ2

Amyloid fibril (in vitro) from full-length hnRNPA1 protein

Summary for 7ZJ2

• Entry DOI: 10.2210/pdb7zj2/pdb
• EMDB information: 14739
• Descriptor: Isoform A1-A of Heterogeneous nuclear ribonucleoprotein A1 (1 entity in total)
• Functional Keywords: amyloidosis, misfolding disease, inflammation, prion, protein fibril, nuclear protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 410954.72

Authors

Sharma, K.,Banerjee, S.,Schmidt, M.,Faendrich, M. (deposition date: 2022-04-08, release date: 2023-08-02, Last modification date: 2024-07-24)

Primary citation

Sharma, K.,Banerjee, S.,Savran, D.,Rajes, C.,Wiese, S.,Girdhar, A.,Schwierz, N.,Lee, C.,Shorter, J.,Schmidt, M.,Guo, L.,Fandrich, M.
Cryo-EM Structure of the Full-length hnRNPA1 Amyloid Fibril.
J.Mol.Biol., 435:168211-168211, 2023

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 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.

PubMed: 37481159
DOI: 10.1016/j.jmb.2023.168211

Experimental method

ELECTRON MICROSCOPY (3.32 Å)