A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform

David Peretz; R. Anthony Williamson; Yoichi Matsunaga; Hana Serban; Clemencia Pinilla; Raiza B. Bastidas; Roman Rozenshteyn; Thomas L. James; Richard A. Houghten; Fred E. Cohen; Stanley B. Prusiner; Dennis R. Burton

doi:10.1006/jmbi.1997.1328

A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform

David Peretz, R. Anthony Williamson, Yoichi Matsunaga, Hana Serban, Clemencia Pinilla, Raiza B. Bastidas, Roman Rozenshteyn, Thomas L. James, Richard A. Houghten, Fred E. Cohen, Stanley B. Prusiner, Dennis R. Burton

Research output: Contribution to journal › Article › peer-review

324 Scopus citations

Abstract

The scrapie prion protein (PrP(Sc)) is formed from the cellular isoform (PrP(C)) by a post-translational process that involves a profound conformational change. Linear epitopes for recombinant antibody Fab fragments (Fabs) on PrP(C) and on the protease-resistant core of PrP(Sc), designated PrP 27-30, were identified using ELISA and immunoprecipitation. An epitope region at the C terminus was accessible in both PrP(C) and PrP 27-30; in contrast, epitopes towards the N-terminal region (residues 90 to 120) were accessible in PrP(C) but largely cryptic in PrP 27-30. Denaturation of PrP 27-30 exposed the epitopes of the N-terminal domain. We argue from our findings that the major conformational change underlying PrP(Sc) formation occurs within the N-terminal segment of PrP 27-30.

Original language	English (US)
Pages (from-to)	614-622
Number of pages	9
Journal	Journal of Molecular Biology
Volume	273
Issue number	3
DOIs	https://doi.org/10.1006/jmbi.1997.1328
State	Published - Oct 31 1997
Externally published	Yes

Keywords

Conformational rearrangement
Liposome
Prion disease
Recombinant antibody
Scrapie

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10.1006/jmbi.1997.1328

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Peretz, D., Williamson, R. A., Matsunaga, Y., Serban, H., Pinilla, C., Bastidas, R. B., Rozenshteyn, R., James, T. L., Houghten, R. A., Cohen, F. E., Prusiner, S. B., & Burton, D. R. (1997). A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform. Journal of Molecular Biology, 273(3), 614-622. https://doi.org/10.1006/jmbi.1997.1328

Peretz, D, Williamson, RA, Matsunaga, Y, Serban, H, Pinilla, C, Bastidas, RB, Rozenshteyn, R, James, TL, Houghten, RA, Cohen, FE, Prusiner, SB & Burton, DR 1997, 'A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform', Journal of Molecular Biology, vol. 273, no. 3, pp. 614-622. https://doi.org/10.1006/jmbi.1997.1328

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title = "A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform",

abstract = "The scrapie prion protein (PrP(Sc)) is formed from the cellular isoform (PrP(C)) by a post-translational process that involves a profound conformational change. Linear epitopes for recombinant antibody Fab fragments (Fabs) on PrP(C) and on the protease-resistant core of PrP(Sc), designated PrP 27-30, were identified using ELISA and immunoprecipitation. An epitope region at the C terminus was accessible in both PrP(C) and PrP 27-30; in contrast, epitopes towards the N-terminal region (residues 90 to 120) were accessible in PrP(C) but largely cryptic in PrP 27-30. Denaturation of PrP 27-30 exposed the epitopes of the N-terminal domain. We argue from our findings that the major conformational change underlying PrP(Sc) formation occurs within the N-terminal segment of PrP 27-30.",

keywords = "Conformational rearrangement, Liposome, Prion disease, Recombinant antibody, Scrapie",

author = "David Peretz and Williamson, {R. Anthony} and Yoichi Matsunaga and Hana Serban and Clemencia Pinilla and Bastidas, {Raiza B.} and Roman Rozenshteyn and James, {Thomas L.} and Houghten, {Richard A.} and Cohen, {Fred E.} and Prusiner, {Stanley B.} and Burton, {Dennis R.}",

year = "1997",

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doi = "10.1006/jmbi.1997.1328",

language = "English (US)",

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T1 - A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform

AU - Peretz, David

AU - Williamson, R. Anthony

AU - Matsunaga, Yoichi

AU - Serban, Hana

AU - Pinilla, Clemencia

AU - Bastidas, Raiza B.

AU - Rozenshteyn, Roman

AU - James, Thomas L.

AU - Houghten, Richard A.

AU - Cohen, Fred E.

AU - Prusiner, Stanley B.

AU - Burton, Dennis R.

PY - 1997/10/31

Y1 - 1997/10/31

N2 - The scrapie prion protein (PrP(Sc)) is formed from the cellular isoform (PrP(C)) by a post-translational process that involves a profound conformational change. Linear epitopes for recombinant antibody Fab fragments (Fabs) on PrP(C) and on the protease-resistant core of PrP(Sc), designated PrP 27-30, were identified using ELISA and immunoprecipitation. An epitope region at the C terminus was accessible in both PrP(C) and PrP 27-30; in contrast, epitopes towards the N-terminal region (residues 90 to 120) were accessible in PrP(C) but largely cryptic in PrP 27-30. Denaturation of PrP 27-30 exposed the epitopes of the N-terminal domain. We argue from our findings that the major conformational change underlying PrP(Sc) formation occurs within the N-terminal segment of PrP 27-30.

AB - The scrapie prion protein (PrP(Sc)) is formed from the cellular isoform (PrP(C)) by a post-translational process that involves a profound conformational change. Linear epitopes for recombinant antibody Fab fragments (Fabs) on PrP(C) and on the protease-resistant core of PrP(Sc), designated PrP 27-30, were identified using ELISA and immunoprecipitation. An epitope region at the C terminus was accessible in both PrP(C) and PrP 27-30; in contrast, epitopes towards the N-terminal region (residues 90 to 120) were accessible in PrP(C) but largely cryptic in PrP 27-30. Denaturation of PrP 27-30 exposed the epitopes of the N-terminal domain. We argue from our findings that the major conformational change underlying PrP(Sc) formation occurs within the N-terminal segment of PrP 27-30.

KW - Conformational rearrangement

KW - Liposome

KW - Prion disease

KW - Recombinant antibody

KW - Scrapie

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JF - Journal of Molecular Biology

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ER -

A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform

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