8efu

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a22L prion fibril

Structural highlights

8efu is a 5 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Prion strains in a given type of mammalian host are distinguished by differences in clinical presentation, neuropathological lesions, survival time, and characteristics of the infecting prion protein (PrP) assemblies. Near-atomic structures of prions from two host species with different PrP sequences have been determined but comparisons of distinct prion strains of the same amino acid sequence are needed to identify purely conformational determinants of prion strain characteristics. Here we report a 3.2 A resolution cryogenic electron microscopy-based structure of the 22L prion strain purified from the brains of mice engineered to express only PrP lacking glycophosphatidylinositol anchors [anchorless (a) 22L]. Comparison of this near-atomic structure to our recently determined structure of the aRML strain propagated in the same inbred mouse reveals that these two mouse prion strains have distinct conformational templates for growth via incorporation of PrP molecules of the same sequence. Both a22L and aRML are assembled as stacks of PrP molecules forming parallel in-register intermolecular beta-sheets and intervening loops, with single monomers spanning the ordered fibril core. Each monomer shares an N-terminal steric zipper, three major arches, and an overall V-shape, but the details of these and other conformational features differ markedly. Thus, variations in shared conformational motifs within a parallel in-register beta-stack fibril architecture provide a structural basis for prion strain differentiation within a single host genotype.

Cryo-EM of prion strains from the same genotype of host identifies conformational determinants.,Hoyt F, Alam P, Artikis E, Schwartz CL, Hughson AG, Race B, Baune C, Raymond GJ, Baron GS, Kraus A, Caughey B PLoS Pathog. 2022 Nov 7;18(11):e1010947. doi: 10.1371/journal.ppat.1010947. , eCollection 2022 Nov. PMID:36342968[5]

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

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Citations
4 reviews cite this structure
Beyond Strains: Molecular Diversity in Alpha-Synuclein at the Center of Disease Heterogeneity.
Wojewska et al. (2023)
3 more
6 other articles
No citations found

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ Hoyt F, Alam P, Artikis E, Schwartz CL, Hughson AG, Race B, Baune C, Raymond GJ, Baron GS, Kraus A, Caughey B. Cryo-EM of prion strains from the same genotype of host identifies conformational determinants. PLoS Pathog. 2022 Nov 7;18(11):e1010947. PMID:36342968 doi:10.1371/journal.ppat.1010947

Contents


PDB ID 8efu

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