Modeling of a propagation mechanism of infectious prion protein; a hexamer as the minimum infectious unit

Hironori K. Nakamura; Mitsunori Takano; Kazuo Kuwata

doi:10.1016/j.bbrc.2007.07.103

Modeling of a propagation mechanism of infectious prion protein; a hexamer as the minimum infectious unit

Hironori K. Nakamura, Mitsunori Takano, Kazuo Kuwata^*

^*この研究の対応する著者

先進理工学部

研究成果: Article › 査読

3 被引用数 (Scopus)

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To construct a new model of the propagation mechanism of infectious scrapie-type prion protein (PrP^Sc), here we conducted a disruption simulation of a PrP^Sc nonamer using structure-based molecular dynamics simulation method based on a hypothetical PrP^Sc model structure. The simulation results showed that the nonamer disrupted in cooperative manners into monomers via two significant intermediate states: (1) a nonamer with a partially unfolded surface trimer and (2) a hexamer and three monomers. Dimers and trimers were rarely observed. Then, we propose a new PrP^Sc propagation mechanism where a hexamer plays an essential role as a minimum infectious unit.

本文言語	English
ページ（範囲）	789-793
ページ数	5
ジャーナル	Biochemical and Biophysical Research Communications
巻	361
号	3
DOI	https://doi.org/10.1016/j.bbrc.2007.07.103
出版ステータス	Published - 2007 9月 28

ASJC Scopus subject areas

生物理学
生化学
分子生物学
細胞生物学

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10.1016/j.bbrc.2007.07.103

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@article{56c60ad03e824a2fb9142f0314f55833,

title = "Modeling of a propagation mechanism of infectious prion protein; a hexamer as the minimum infectious unit",

abstract = "To construct a new model of the propagation mechanism of infectious scrapie-type prion protein (PrPSc), here we conducted a disruption simulation of a PrPSc nonamer using structure-based molecular dynamics simulation method based on a hypothetical PrPSc model structure. The simulation results showed that the nonamer disrupted in cooperative manners into monomers via two significant intermediate states: (1) a nonamer with a partially unfolded surface trimer and (2) a hexamer and three monomers. Dimers and trimers were rarely observed. Then, we propose a new PrPSc propagation mechanism where a hexamer plays an essential role as a minimum infectious unit.",

keywords = "Amyloid, Coarse-grained model, Go model, Molecular dynamics, Prion disease",

author = "Nakamura, {Hironori K.} and Mitsunori Takano and Kazuo Kuwata",

note = "Funding Information: We thank Nobuyasu Koga, Fumiko Takagi, and Shoji Takada for providing the computer program for the Go model, C{\'e}dric Govaerts for providing the coordinates of the model PrP Sc structure, and Thomas L. James for helpful discussions. This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation.",

year = "2007",

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doi = "10.1016/j.bbrc.2007.07.103",

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T1 - Modeling of a propagation mechanism of infectious prion protein; a hexamer as the minimum infectious unit

AU - Nakamura, Hironori K.

AU - Takano, Mitsunori

AU - Kuwata, Kazuo

N1 - Funding Information: We thank Nobuyasu Koga, Fumiko Takagi, and Shoji Takada for providing the computer program for the Go model, Cédric Govaerts for providing the coordinates of the model PrP Sc structure, and Thomas L. James for helpful discussions. This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation.

PY - 2007/9/28

Y1 - 2007/9/28

N2 - To construct a new model of the propagation mechanism of infectious scrapie-type prion protein (PrPSc), here we conducted a disruption simulation of a PrPSc nonamer using structure-based molecular dynamics simulation method based on a hypothetical PrPSc model structure. The simulation results showed that the nonamer disrupted in cooperative manners into monomers via two significant intermediate states: (1) a nonamer with a partially unfolded surface trimer and (2) a hexamer and three monomers. Dimers and trimers were rarely observed. Then, we propose a new PrPSc propagation mechanism where a hexamer plays an essential role as a minimum infectious unit.

AB - To construct a new model of the propagation mechanism of infectious scrapie-type prion protein (PrPSc), here we conducted a disruption simulation of a PrPSc nonamer using structure-based molecular dynamics simulation method based on a hypothetical PrPSc model structure. The simulation results showed that the nonamer disrupted in cooperative manners into monomers via two significant intermediate states: (1) a nonamer with a partially unfolded surface trimer and (2) a hexamer and three monomers. Dimers and trimers were rarely observed. Then, we propose a new PrPSc propagation mechanism where a hexamer plays an essential role as a minimum infectious unit.

KW - Amyloid

KW - Coarse-grained model

KW - Go model

KW - Molecular dynamics

KW - Prion disease

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DO - 10.1016/j.bbrc.2007.07.103

M3 - Article

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AN - SCOPUS:34547797445

SN - 0006-291X

VL - 361

SP - 789

EP - 793

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Modeling of a propagation mechanism of infectious prion protein; a hexamer as the minimum infectious unit

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