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^*

^*Corresponding author for this work

School of Advanced Science and Engineering

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

3 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	789-793
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	361
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2007.07.103
Publication status	Published - 2007 Sept 28

Keywords

Amyloid
Coarse-grained model
Go model
Molecular dynamics
Prion disease

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2007.07.103

Cite this

@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",

month = sep,

day = "28",

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

language = "English",

volume = "361",

pages = "789--793",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "3",

}

TY - JOUR

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

UR - http://www.scopus.com/inward/record.url?scp=34547797445&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547797445&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2007.07.103

DO - 10.1016/j.bbrc.2007.07.103

M3 - Article

C2 - 17678874

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this