Genetic influence on the structural variations of the abnormal prion protein

Piero Parchi, Wenquan Zou, Wen Wang, Paul Brown, Sabina Capellari, Bernardino Ghetti, Nicolas Kopp, Walter J. Schulz-Schaeffer, Hans A. Kretzschmar, Mark W. Head, James W. Ironside, Pierluigi Gambetti, Shu G. Chen

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

Prion diseases are characterized by the presence of the abnormal prion protein PrP(Sc), which is believed to be generated by the conversion of the α-helical structure that predominates in the normal PrP isoform into a β-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrP(Sc), type 1 and 2, can be distinguished based on the difference in electrophoretic migration of the PK-resistant core fragment. In this study, protein sequencing was used to identify the PK cleavage sites of PrP(Sc) in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrP(Sc), respectively, and numerous secondary cleavages distributed along the region spanning residues 74-102. Accordingly, we identify three regions in PrP(Sc): one N-terminal (residues 23-73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is invariably PK-resistant, and a third variable region (residues 74-102) where the site of the PK cleavage, likely reflecting the extent of the β-sheet structure, varies mostly as a function of the PrP genotype at codon 129.

Original languageEnglish
Pages (from-to)10168-10172
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number18
StatePublished - Aug 29 2000

Fingerprint

Endopeptidase K
Prion Diseases
Protein Sequence Analysis
Codon
Prion Proteins
Protein Isoforms
Genotype

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Genetic influence on the structural variations of the abnormal prion protein. / Parchi, Piero; Zou, Wenquan; Wang, Wen; Brown, Paul; Capellari, Sabina; Ghetti, Bernardino; Kopp, Nicolas; Schulz-Schaeffer, Walter J.; Kretzschmar, Hans A.; Head, Mark W.; Ironside, James W.; Gambetti, Pierluigi; Chen, Shu G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 18, 29.08.2000, p. 10168-10172.

Research output: Contribution to journalArticle

Parchi, P, Zou, W, Wang, W, Brown, P, Capellari, S, Ghetti, B, Kopp, N, Schulz-Schaeffer, WJ, Kretzschmar, HA, Head, MW, Ironside, JW, Gambetti, P & Chen, SG 2000, 'Genetic influence on the structural variations of the abnormal prion protein', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 18, pp. 10168-10172.
Parchi, Piero ; Zou, Wenquan ; Wang, Wen ; Brown, Paul ; Capellari, Sabina ; Ghetti, Bernardino ; Kopp, Nicolas ; Schulz-Schaeffer, Walter J. ; Kretzschmar, Hans A. ; Head, Mark W. ; Ironside, James W. ; Gambetti, Pierluigi ; Chen, Shu G. / Genetic influence on the structural variations of the abnormal prion protein. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 18. pp. 10168-10172.
@article{6ed71eae345a4874b9ee517744360abe,
title = "Genetic influence on the structural variations of the abnormal prion protein",
abstract = "Prion diseases are characterized by the presence of the abnormal prion protein PrP(Sc), which is believed to be generated by the conversion of the α-helical structure that predominates in the normal PrP isoform into a β-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrP(Sc), type 1 and 2, can be distinguished based on the difference in electrophoretic migration of the PK-resistant core fragment. In this study, protein sequencing was used to identify the PK cleavage sites of PrP(Sc) in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrP(Sc), respectively, and numerous secondary cleavages distributed along the region spanning residues 74-102. Accordingly, we identify three regions in PrP(Sc): one N-terminal (residues 23-73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is invariably PK-resistant, and a third variable region (residues 74-102) where the site of the PK cleavage, likely reflecting the extent of the β-sheet structure, varies mostly as a function of the PrP genotype at codon 129.",
author = "Piero Parchi and Wenquan Zou and Wen Wang and Paul Brown and Sabina Capellari and Bernardino Ghetti and Nicolas Kopp and Schulz-Schaeffer, {Walter J.} and Kretzschmar, {Hans A.} and Head, {Mark W.} and Ironside, {James W.} and Pierluigi Gambetti and Chen, {Shu G.}",
year = "2000",
month = "8",
day = "29",
language = "English",
volume = "97",
pages = "10168--10172",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "18",

}

TY - JOUR

T1 - Genetic influence on the structural variations of the abnormal prion protein

AU - Parchi, Piero

AU - Zou, Wenquan

AU - Wang, Wen

AU - Brown, Paul

AU - Capellari, Sabina

AU - Ghetti, Bernardino

AU - Kopp, Nicolas

AU - Schulz-Schaeffer, Walter J.

AU - Kretzschmar, Hans A.

AU - Head, Mark W.

AU - Ironside, James W.

AU - Gambetti, Pierluigi

AU - Chen, Shu G.

PY - 2000/8/29

Y1 - 2000/8/29

N2 - Prion diseases are characterized by the presence of the abnormal prion protein PrP(Sc), which is believed to be generated by the conversion of the α-helical structure that predominates in the normal PrP isoform into a β-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrP(Sc), type 1 and 2, can be distinguished based on the difference in electrophoretic migration of the PK-resistant core fragment. In this study, protein sequencing was used to identify the PK cleavage sites of PrP(Sc) in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrP(Sc), respectively, and numerous secondary cleavages distributed along the region spanning residues 74-102. Accordingly, we identify three regions in PrP(Sc): one N-terminal (residues 23-73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is invariably PK-resistant, and a third variable region (residues 74-102) where the site of the PK cleavage, likely reflecting the extent of the β-sheet structure, varies mostly as a function of the PrP genotype at codon 129.

AB - Prion diseases are characterized by the presence of the abnormal prion protein PrP(Sc), which is believed to be generated by the conversion of the α-helical structure that predominates in the normal PrP isoform into a β-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrP(Sc), type 1 and 2, can be distinguished based on the difference in electrophoretic migration of the PK-resistant core fragment. In this study, protein sequencing was used to identify the PK cleavage sites of PrP(Sc) in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrP(Sc), respectively, and numerous secondary cleavages distributed along the region spanning residues 74-102. Accordingly, we identify three regions in PrP(Sc): one N-terminal (residues 23-73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is invariably PK-resistant, and a third variable region (residues 74-102) where the site of the PK cleavage, likely reflecting the extent of the β-sheet structure, varies mostly as a function of the PrP genotype at codon 129.

UR - http://www.scopus.com/inward/record.url?scp=12944253111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12944253111&partnerID=8YFLogxK

M3 - Article

C2 - 10963679

AN - SCOPUS:12944253111

VL - 97

SP - 10168

EP - 10172

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 18

ER -