Structural highlights
Disease
[PRIO_MOUSE] Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc.
Function
[PRIO_MOUSE] May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (By similarity). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains.[1] [2] [3] [4]
Publication Abstract from PubMed
Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains.
2.7 A cryo-EM structure of ex vivo RML prion fibrils.,Manka SW, Zhang W, Wenborn A, Betts J, Joiner S, Saibil HR, Collinge J, Wadsworth JDF Nat Commun. 2022 Jul 13;13(1):4004. doi: 10.1038/s41467-022-30457-7. PMID:35831275[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mani K, Cheng F, Havsmark B, Jonsson M, Belting M, Fransson LA. Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-nitroso-dependent autocleavage of glypican-1 heparan sulfate. J Biol Chem. 2003 Oct 3;278(40):38956-65. Epub 2003 May 5. PMID:12732622 doi:10.1074/jbc.M300394200
- ↑ Steele AD, Emsley JG, Ozdinler PH, Lindquist S, Macklis JD. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3416-21. Epub 2006 Feb 21. PMID:16492732 doi:10.1073/pnas.0511290103
- ↑ Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009 Feb 26;457(7233):1128-32. doi: 10.1038/nature07761. PMID:19242475 doi:10.1038/nature07761
- ↑ Singh A, Kong Q, Luo X, Petersen RB, Meyerson H, Singh N. Prion protein (PrP) knock-out mice show altered iron metabolism: a functional role for PrP in iron uptake and transport. PLoS One. 2009 Jul 1;4(7):e6115. doi: 10.1371/journal.pone.0006115. PMID:19568430 doi:10.1371/journal.pone.0006115
- ↑ Manka SW, Zhang W, Wenborn A, Betts J, Joiner S, Saibil HR, Collinge J, Wadsworth JDF. 2.7 A cryo-EM structure of ex vivo RML prion fibrils. Nat Commun. 2022 Jul 13;13(1):4004. doi: 10.1038/s41467-022-30457-7. PMID:35831275 doi:http://dx.doi.org/10.1038/s41467-022-30457-7
