7zj2

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

Structural highlights

7zj2 is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.32Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ROA1_HUMAN Amyotrophic lateral sclerosis;Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.[1] The disease is caused by mutations affecting the gene represented in this entry.[2]

Function

ROA1_HUMAN Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.[3]

Publication Abstract from PubMed

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(1) 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.

Cryo-EM Structure of the Full-length hnRNPA1 Amyloid Fibril.,Sharma K, Banerjee S, Savran D, Rajes C, Wiese S, Girdhar A, Schwierz N, Lee C, Shorter J, Schmidt M, Guo L, Fandrich M J Mol Biol. 2023 Sep 15;435(18):168211. doi: 10.1016/j.jmb.2023.168211. Epub 2023 , Jul 20. PMID:37481159[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
2 reviews cite this structure
Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD.
Khalil et al. (2024)
1 more
1 other articles
No citations found

See Also

References

  1. ↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
  2. ↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
  3. ↑ Kim CS, Seol SK, Song OK, Park JH, Jang SK. An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication. J Virol. 2007 Apr;81(8):3852-65. Epub 2007 Jan 17. PMID:17229681 doi:http://dx.doi.org/10.1128/JVI.01311-06
  4. ↑ Sharma K, Banerjee S, Savran D, Rajes C, Wiese S, Girdhar A, Schwierz N, Lee C, Shorter J, Schmidt M, Guo L, Fändrich M. Cryo-EM Structure of the Full-length hnRNPA1 Amyloid Fibril. J Mol Biol. 2023 Jul 20;435(18):168211. PMID:37481159 doi:10.1016/j.jmb.2023.168211

Contents


PDB ID 7zj2

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