Insoluble wild–type and protease–resistant mutant prion protein in brains of patients with inherited prion disease

1996 ◽  
Vol 2 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Ruth Gabizon ◽  
Glenn Telling ◽  
Zeev Meiner ◽  
Michele Halimi ◽  
Irit Kahana ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Resistant Mutant ◽  
Wild Type

scholarly journals Recombinant prion protein induces a new transmissible prion disease in wild-type animals

2010 ◽  
Vol 119 (2) ◽  
pp. 177-187 ◽  
Author(s):  
Natallia Makarava ◽  
Gabor G. Kovacs ◽  
Olga Bocharova ◽  
Regina Savtchenko ◽  
Irina Alexeeva ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Wild Type ◽  
Recombinant Prion Protein

scholarly journals CHROMOSOMAL BASIS OF THE MEROZYGOSITY IN A PARTIALLY DIPLOID MUTANT OF PNEUMOCOCCUS

Genetics ◽  
1975 ◽  
Vol 80 (4) ◽  
pp. 667-678
Author(s):  
Mary Lee S Ledbetter ◽  
Rollin D Hotchkiss
Keyword(s):  
High Efficiency ◽  
Point Mutations ◽  
Resistant Mutant ◽  
Chromosomal Marker ◽  
Structural Abnormality ◽  
C Cells ◽  
Wild Type ◽  
Chromosomal Locus ◽  
Low Efficiency ◽  
Derivatives Of

ABSTRACT A sulfonamide-resistant mutant of pneumococcus, sulr-c, displays a genetic instability, regularly segregating to wild type. DNA extracts of derivatives of the strain possess transforming activities for both the mutant and wild-type alleles, establishing that the strain is a partial diploid. The linkage of sulr-c to strr-61, a stable chromosomal marker, was established, thus defining a chromosomal locus for sulr-c. DNA isolated from sulr-c cells transforms two mutant recipient strains at the same low efficiency as it does a wild-type recipient, although the mutant property of these strains makes them capable of integrating classical "low-efficiency" donor markers equally as efficiently as "high efficiency" markers. Hence sulr-c must have a different basis for its low efficiency than do classical low efficiency point mutations. We suggest that the DNA in the region of the sulr-c mutation has a structural abnormality which leads both to its frequent segregation during growth and its difficulty in efficiently mediating genetic transformation.

scholarly journals The First Report of the Prion Protein Gene (PRNP) Sequence in Pekin Ducks (Anas platyrhynchos domestica): The Potential Prion Disease Susceptibility in Ducks

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 193
Author(s):  
Min-Ju Jeong ◽  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Prion Protein ◽  
Dna Sequence ◽  
Prion Disease ◽  
Protein Gene ◽  
Prnp Gene ◽  
Pekin Duck ◽  
Prion Protein Gene ◽  
First Report ◽  
Aggregation Propensity ◽  
Pekin Ducks

Pathogenic prion protein (PrPSc), converted from normal prion protein (PrPC), causes prion disease. Although prion disease has been reported in several mammalian species, chickens are known to show strong resistance to prion diseases. In addition to chickens, the domestic duck occupies a large proportion in the poultry industry and may be regarded as a potential resistant host against prion disease. However, the DNA sequence of the prion protein gene (PRNP) has not been reported in domestic ducks. Here, we performed amplicon sequencing targeting the duck PRNP gene with the genomic DNA of Pekin ducks. In addition, we aligned the PrP sequence of the Pekin duck with that of various species using ClustalW2 and carried out phylogenetic analysis using Molecular Evolutionary Genetics Analysis X (MEGA X). We also constructed the structural modeling of the tertiary and secondary structures in avian PrP using SWISS-MODEL. Last, we investigated the aggregation propensity on Pekin duck PrP using AMYCO. We first reported the DNA sequence of the PRNP gene in Pekin ducks and found that the PrP sequence of Pekin ducks is more similar to that of geese than to that of chickens and mallards (wild ducks). Interestingly, Pekin duck PrP showed a high proportion of β-sheets compared to that of chicken PrP, and a high aggregation propensity compared to that of avian PrPs. However, Pekin duck PrP with substitutions of chicken-specific amino acids showed reduced aggregation propensities. To the best of our knowledge, this is the first report on the genetic characteristics of the PRNP sequence in Pekin ducks.

Detection of cutaneous prion protein deposits could help diagnose GPI‐anchorless prion disease with neuropathy

2021 ◽  
Author(s):  
Hiroyuki Honda ◽  
Kosuke Matsuzono ◽  
Kota Satoh ◽  
Masayoshi Fujisawa ◽  
Satoshi O. Suzuki ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Deposits

scholarly journals Doxycycline control of prion protein transgene expression modulates prion disease in mice

1998 ◽  
Vol 95 (21) ◽  
pp. 12580-12585 ◽  
Author(s):  
P. Tremblay ◽  
Z. Meiner ◽  
M. Galou ◽  
C. Heinrich ◽  
C. Petromilli ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Transgene Expression

scholarly journals Combining mutations that modulate inter-subunit interactions and proteolytic inactivation enhance the stability of factor VIIIa

2014 ◽  
Vol 112 (07) ◽  
pp. 43-52 ◽  
Author(s):  
Hironao Wakabayashi ◽  
Jennifer M. Wintermute ◽  
Philip J. Fay
Keyword(s):  
Thermal Stability ◽  
Thrombin Generation ◽  
Resistant Mutant ◽  
Decay Rates ◽  
Single Type ◽  
Wild Type ◽  
Subunit Interactions ◽  
Factor Viiia ◽  
The Stability ◽  
A3 Subunit

SummaryFVIIIa is labile due to the dissociation of A2 subunit. Previously, we introduced hydrophobic mutations at select A1/A2/A3 subunit interfaces yielding more stable FVIII(a) variants. Separately we showed that altering the sequence flanking the primary FXa cleavage site in FVIIIa (Arg336) yielded reduced rates of proteolytic inactivation of FVIIIa. In this study we prepared the FXa-cleavage resistant mutant (336(P4-P3’)562) combined with mutations of Ala108Ile, Asp519Val/ Glu665Val or Ala108Ile/Asp519Val/Glu665Val and examined the effects of these combinations relative to FVIII thermal stability, rates of FVIIIa decay and proteolytic inactivation of FVIIIa by FXa. Thermal decay rates for 336(P4-P3’)562/Ala108Ile, 336(P4-P3’)562/Asp519Val/ Glu665Val, and 336(P4-P3’)562/Ala108Ile/Asp519Val/Glu665Val variants were reduced by ∼2– to 5-fold as compared with wild-type (WT) primarily reflecting the effects of the A domain interface mutations. FVIIIa decay rates for 336(P4-P3’)562/Asp519Val/Glu665Val and 336(P4-P3’)562/Ala108Ile/Asp519Val/Glu665Val variants were reduced by ∼25 fold, indicating greater stability than the control Asp519Val/Glu665Val variant (∼14-fold). Interestingly, 336(P4-P3’)562/Asp519Val/Glu665Val and 336(P4-P3’)562/Ala108Ile/ Asp519Val/Glu665Val variants showed reduced FXa-inactivation rates compared with the 336(P4-P3’)562 control (∼4-fold), suggesting A2 subunit destabilisation is a component of proteolytic inactivation. Thrombin generation assays using the combination variants were similar to the Asp519Val/Glu665Val control. These results indicate that combining multiple gain-of-function FVIII mutations yields FVIII variants with increased stability relative to a single type of mutation.

scholarly journals Genetic human prion disease modelled in PrP transgenic Drosophila

2017 ◽  
Vol 474 (19) ◽  
pp. 3253-3267 ◽  
Author(s):  
Alana M. Thackray ◽  
Alzbeta Cardova ◽  
Hanna Wolf ◽  
Lydia Pradl ◽  
Ina Vorberg ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Principal Component ◽  
Site Directed Mutagenesis ◽  
Host Protein ◽  
Therapeutic Interventions ◽  
Proteinase K ◽  
Human Prion Disease ◽  
Transgenic Drosophila

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt–Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrPSc, an abnormal isomer of the normal host protein PrPC, in the brain of affected individuals. PrPSc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila. We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila. Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host.

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