2008年12月
Critical Region for Amyloid Fibril Formation of Mouse Prion Protein: Unusual Amyloidogenic Properties of the Helix 2 Peptide
BIOCHEMISTRY
- ,
- ,
- 巻
- 47
- 号
- 50
- 開始ページ
- 13242
- 終了ページ
- 13251
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1021/bi801562w
- 出版者・発行元
- AMER CHEMICAL SOC
To gain insight into the structural mechanism of the conformational conversion process of prion, we examined the potential amyloidogenic property of each secondary structural element in a mouse prion protein (mPrP) and discriminated their relative significance for the formation of amyloid fibrils. Although peptides corresponding to alpha-helix 2 and alpha-helix 3 (named H2 peptide and H3 peptide, respectively) formed the amyloid-like fibrils, their structures were quite different. H2 fibrils formed the ordered beta-sheet with the beta-turn conformation, and the resultant fibrils were long and straight. In contrast, H3 fibrils consisted of the beta-sheet with the random conformation, and the resultant fibrils were short and flexible. These properties are basically consistent with their hydrophobicity and beta-strand propensity profiles. To examine the cross reactivity between peptide fragments and full-length mPrP, we then carried out seeding experiments. While H2 seeds induced the formation of fibrils of full-length mPrP as quickly as full-length mPrP seeds, H3 seeds exhibited a long lag time. This implies that the region of alpha-helix 2 rather than alpha-helix 3 in mPrP has great potential for initiating fibril formation. As a whole, the alpha-helix 2 region would be crucial for the nucleation-dependent replication process of the prion protein.
- リンク情報
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- DOI
- https://doi.org/10.1021/bi801562w
- CiNii Articles
- http://ci.nii.ac.jp/naid/80020036405
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/19053276
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000261510500013&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1021/bi801562w
- ISSN : 0006-2960
- CiNii Articles ID : 80020036405
- PubMed ID : 19053276
- Web of Science ID : WOS:000261510500013