ライフサイエンスコーパス: PrP-sen

1 PrP-sen association with SCRLs was pH-independent.

2 PrP-sen is attached to the cell membrane by a glycosylph

3 PrP-sen was also one of a small subset of phosphatidylin

4 n part, explain the observation that not all PrP-sen-expressing cells appear to support transmissible

5 Cells expressing anchored PrP-sen produced PrP-res after exposure to 22L.

6 , scrapie-infected cells expressing anchored PrP-sen transmitted disease to mice whereas cells expres

7 TSE infection, cells expressing GPI-anchored PrP-sen, anchorless PrP-sen, or both forms of PrP-sen we

8 ecause transgenic mice expressing anchorless PrP-sen accumulate PrP-res and replicate infectivity.

9 to mice whereas cells expressing anchorless PrP-sen alone did not.

10 ata suggest that cells expressing anchorless PrP-sen are not directly infected with scrapie.

11 prisingly, while cells expressing anchorless PrP-sen made anchorless PrP-res in the first 96 h postin

12 ion in transgenic mice expressing anchorless PrP-sen may be occurring extracellularly.

13 expressing GPI-anchored PrP-sen, anchorless PrP-sen, or both forms of PrP-sen were exposed to the mo

14 y mimic contact surfaces between PrP-res and PrP-sen and thereby serve as models of potential therape

15 o acid sequence homology between PrP-res and PrP-sen is important in the formation of new PrP-res and

16 omposed predominantly of hamster PrP-res and PrP-sen.

17 Interestingly, DRM-associated PrP-sen was not converted to PrP-res until the PrP-sen w

18 Rather, homology between PrP-sen and hamster PrP-res at amino acid residue 155 de

19 was strongly influenced by homology between PrP-sen and PrP-res at amino acid residue 138, a residue

20 dies to map the sites of interaction between PrP-sen and PrP-res.

21 further intermolecular interactions between PrP-sen and PrP-res are required to complete the process

22 and subsequent conversion reactions between PrP-sen and PrP-res.

23 While amino acid sequence similarity between PrP-sen and PrP-res influences both PrP-res formation an

24 sed to measure the interaction of SCRL-bound PrP-sen with exogenous PrP-res as contained in microsome

25 CWD)-induced conversions of human and bovine PrP-sen were much less efficient, and conversion of ovin

26 he two forms of raft membrane association by PrP-sen, only the GPI anchor-directed form resists conve

27 induces the conversion of recombinant cervid PrP-sen molecules to the protease-resistant state in acc

28 We constructed PrP-sen mutants with deletions of the first beta-strand,

29 d its normal protease-sensitive counterpart, PrP-sen or PrP(C).

30 hamster PrP-sen, which, unlike brain-derived PrP-sen, can be easily concentrated, mutated and synthet

31 s of different animal species have different PrP-sen structural requirements for the efficient format

32 t does not include the epitope in the folded PrP-sen structure.

33 SCRL-bound GPI(+) PrP-sen was not converted to PrP-res until PI-PLC was ad

34 However, only GPI(+) PrP-sen resisted extraction with cold Triton X-100.

35 In contrast, SCRL-bound GPI(-) PrP-sen was converted to PrP-res without PI-PLC or PEG t

36 h (GPI(+)) and GPI anchor-deficient (GPI(-)) PrP-sen produced in fibroblasts stably associated with S

37 ntrast in mouse neuroblastoma cells, hamster PrP-sen with 5, 9, and 11 octapeptide repeats were expre

38 the end of the first alpha helix in hamster PrP-sen; this feature is not present in mouse PrP-sen.

39 This technique uses recombinant hamster PrP-sen, which, unlike brain-derived PrP-sen, can be eas

40 ding of antibodies (alpha219-232) to hamster PrP-sen residues 219-232 inhibited the binding of PrP-se

41 ssion, but both mutant and wild-type hamster PrP-sen molecules demonstrated abnormal properties of ag

42 Our studies showed that heterologous PrP-sen can bind to PrP-res with little conversion to th

43 h molar ratios of homologous to heterologous PrP-sen molecules as low as 1:1.

44 interfere with the conversion of homologous PrP-sen.

45 sion, but not the binding, of the homologous PrP-sen to PrP-res.

46 We found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with bot

47 Here we report that, if PrP-sen and PrP-res are derived from different species,

48 lysulfate induced a conformational change in PrP-sen that may potentiate its PrP-res-induced conversi

49 ted cell cultures have identified regions in PrP-sen that are important in the formation of PrP-res,

50 n the normal protease-sensitive PrP isoform (PrP-sen) and the protease-resistant isoform (PrP-res), a

51 f the normal protease-sensitive PrP isoform (PrP-sen) to the protease-resistant isoform (PrP-res).

52 from the normal protease-sensitive isoform (PrP-sen) appears to be a key event in the pathogenesis o

53 rP-sen; this feature is not present in mouse PrP-sen.

54 P-res formation by influencing the amount of PrP-sen bound to PrP-res, while the amino acid sequence

55 en residues 219-232 inhibited the binding of PrP-sen to PrP-res and the subsequent generation of PK-r

56 rP-res formation, we compared the binding of PrP-sen to PrP-res with its subsequent acquisition of pr

57 roles specifically inhibit the conversion of PrP-sen to PrP-res without apparent cytotoxic effects.

58 giform encephalopathies is the conversion of PrP-sen to PrP-res.

59 ironment are important for the conversion of PrP-sen to PrP-res.

60 the PrP-res induced cell-free conversion of PrP-sen to the protease-resistant state.

61 ontrast, when cells expressing both forms of PrP-sen were exposed to 22L, both anchored and anchorles

62 rP-sen, anchorless PrP-sen, or both forms of PrP-sen were exposed to the mouse scrapie strain 22L.

63 he beta-strands and the first alpha-helix of PrP-sen can fundamentally affect PrP-res formation and/o

64 processing and the cellular localization of PrP-sen, while deletion of the first beta-strand had no

65 owever, antibodies to several other parts of PrP-sen did not inhibit.

66 during TSE infection requires (i) removal of PrP-sen from target cells; (ii) an exchange of membranes

67 the formation of PrP-res, the exact role of PrP-sen secondary structures in the conformational trans

68 to PrP-res, while the amino acid sequence of PrP-sen influenced the amount of PrP-res generated in th

69 which contained purified DRMs as a source of PrP-sen and brain microsomes from scrapie-infected mice

70 eactions and brain homogenate as a source of PrP-sen.

71 subtle changes in the glycosylation state of PrP-sen.

72 ns were introduced into the flexible tail of PrP-sen (23) to determine if this region was required fo

73 ructures in the conformational transition of PrP-sen to PrP-res has not yet been defined.

74 e results demonstrate that the GPI anchor on PrP-sen is important for the persistent infection of cel

75 the localized nature of the binding site on PrP-sen support the idea that PrP-sen serves as a critic

76 144-153) and that the helix is stabilized on PrP-sen by intra-helix salt bridges between two aspartic

77 Only PrP-sen was observed to bind PrP-res.

78 essed normally on the cell surface, but only PrP-sen molecules with 9 or 11 copies of the repeat moti

79 undamentally affect PrP-res formation and/or PrP-sen processing.

80 ions of the tetrapyrrole with PrP-res and/or PrP-sen.

81 ffects on protein biosynthesis in general or PrP-sen biosynthesis in particular.

82 ensitive host glycoprotein, prion protein or PrP-sen, to a protease-resistant form (PrP-res).

83 much less efficient, and conversion of ovine PrP-sen was intermediate.

84 otease-sensitive and glycosylated precursor, PrP-sen.

85 e normal, protease- sensitive prion protein (PrP-sen or PrP(C)) to a protease-resistant form (PrP-res

86 form encephalopathies, normal prion protein (PrP-sen) is converted to a protease-resistant isoform, P

87 f the protease-sensitive host prion protein (PrP-sen) to a protease-resistant isoform (PrP-res) is an

88 on of the normal host-encoded prion protein (PrP-sen) to an abnormal protease-resistant form, PrP-res

89 of normal protease-sensitive prion protein (PrP-sen) to the abnormal protease-resistant form, PrP-re

90 l proteinase K-sensitive host prion protein (PrP-sen) to the abnormal proteinase K-resistant form (Pr

91 se-sensitive form of the host prion protein (PrP-sen).

92 of normal protease-sensitive prion protein (PrP-sen).

93 the normal protease-sensitive prion protein (PrP-sen).

94 roteinase K-sensitive, host-encoded protein, PrP-sen, into its protease-resistant isoform, PrP-res.

95 ormal protease-sensitive host prion protein, PrP-sen, to an abnormal protease-resistant form, PrP-res

96 s the in vitro conversion of the normal PrP (PrP-sen) of another species to the protease-resistant st

97 ular isoform of PrP (protease-sensitive PrP; PrP-sen), the disease-associated isoform (protease-resis

98 Here we show that rabbit PrP-sen does not form PrP-res in murine tissue culture c

99 er PrP-res to convert a panel of recombinant PrP-sen molecules to protease-resistant PrP in a cell-fr

100 During the formation of PrP-res, PrP-sen undergoes conformational changes that involve an

101 ce of a complex interaction between PrP-res, PrP-sen, and the cell and may indicate the cellular comp

102 PrP-res are derived from different species, PrP-sen glycosylation can significantly affect PrP-res f

103 and their respective salt bridges stabilize PrP-sen from converting to PrP-res.

104 salt bridges do not substantially stabilize PrP-sen, the cell-free conversion data suggest that Asp-

105 inding site on PrP-sen support the idea that PrP-sen serves as a critical ligand and/or receptor for

106 P-sen was not converted to PrP-res until the PrP-sen was either released from DRMs by treatment with

107 dues 119-136 inhibit primarily by binding to PrP-sen and blocking its binding to PrP-res.

108 , co- or post-translational modifications to PrP-sen influence PrP-res formation in vitro.

109 f co- or post-translational modifications to PrP-sen is unknown.

110 ected by post-translational modifications to PrP-sen.

111 PrP-res produced from N-terminally truncated PrP-sen.

112 Conversion of unglycosylated PrP-sen appeared to alter both the amount and the confor

113 (PrP-res), a model system was employed using PrP-sen reconstituted into sphingolipid-cholesterol-rich

114 While previous studies in which PrP-sen deletion mutants were expressed in transgenic mi