The importance of steric zipper on the aggregation of the MVGGVV peptide derived from the amyloid β peptide

Liang Kai Chang, Jian Hua Zhao, Hsuan Liang Liu, Josephine W. Wu, Chih Kuang Chuang, Kung Tien Liu, Jenn Tzong Chen, Wei Bor Tsai, Yih Ho

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Amyloid-like fibrils are found in many fatal diseases, such as Alzheimer's disease, Parkinson's disease, type II diabetes mellitus, and prion diseases. Recently, the structural characterization of the MVGGVV peptide from the C-terminal hydrophobic segment of the amyloid-β (Aβ) peptide has revealed a general feature of amyloid-like fibrils, termed as "steric zipper", which is constituted by a tight side-chain complementation of the opposing β-sheet layers. In this study, several all-atom molecular dynamics simulations with explicit water were conducted to investigate the importance of steric zipper on the aggregation of the MVGGVV peptide. Our results show that the structural stability of the MVGGVV oligomers increases with increasing the number of β-strands. We further proposed that the octameric structure (the SH2-ST4 model in this study) is the possible nucleus seed for MVGGVV protofibril formation. Our results also demonstrated that hydrophobic interaction is the principle driving force to stabilize the adjacent β-strands while the steric zipper involved M1, V2, V5 and V6 is responsible for holding the neighboring β-sheet layers together. Finally, a twisted model of the MVGGVV assembly (SH2-ST50), based on the averaged twisted angle of ∼ 11.5° between the adjacent β-strands of the SH2-ST4 model, was proposed. Our results gain insights into the aggregation of the MVGGVV peptide in atomic details and may provide a hint for designing new inhibitors able to prevent the fibril formation of the Aβ peptide.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalJournal of Biomolecular Structure and Dynamics
Volume28
Issue number1
Publication statusPublished - Aug 2010

Fingerprint

Amyloid
Peptides
Prion Diseases
Molecular Dynamics Simulation
Hydrophobic and Hydrophilic Interactions
Type 2 Diabetes Mellitus
Parkinson Disease
Seeds
Alzheimer Disease
Water

Keywords

  • Alzheimer's disease
  • Amyloid fibril
  • Amyloid-β
  • Molecular dynamics (MD) simulation
  • Parkinson's disease
  • Peptide
  • Steric zipper

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

The importance of steric zipper on the aggregation of the MVGGVV peptide derived from the amyloid β peptide. / Chang, Liang Kai; Zhao, Jian Hua; Liu, Hsuan Liang; Wu, Josephine W.; Chuang, Chih Kuang; Liu, Kung Tien; Chen, Jenn Tzong; Tsai, Wei Bor; Ho, Yih.

In: Journal of Biomolecular Structure and Dynamics, Vol. 28, No. 1, 08.2010, p. 39-50.

Research output: Contribution to journalArticle

Chang, LK, Zhao, JH, Liu, HL, Wu, JW, Chuang, CK, Liu, KT, Chen, JT, Tsai, WB & Ho, Y 2010, 'The importance of steric zipper on the aggregation of the MVGGVV peptide derived from the amyloid β peptide', Journal of Biomolecular Structure and Dynamics, vol. 28, no. 1, pp. 39-50.
Chang, Liang Kai ; Zhao, Jian Hua ; Liu, Hsuan Liang ; Wu, Josephine W. ; Chuang, Chih Kuang ; Liu, Kung Tien ; Chen, Jenn Tzong ; Tsai, Wei Bor ; Ho, Yih. / The importance of steric zipper on the aggregation of the MVGGVV peptide derived from the amyloid β peptide. In: Journal of Biomolecular Structure and Dynamics. 2010 ; Vol. 28, No. 1. pp. 39-50.
@article{d4e3fc9563864b388bc3f5cd0984bb0f,
title = "The importance of steric zipper on the aggregation of the MVGGVV peptide derived from the amyloid β peptide",
abstract = "Amyloid-like fibrils are found in many fatal diseases, such as Alzheimer's disease, Parkinson's disease, type II diabetes mellitus, and prion diseases. Recently, the structural characterization of the MVGGVV peptide from the C-terminal hydrophobic segment of the amyloid-β (Aβ) peptide has revealed a general feature of amyloid-like fibrils, termed as {"}steric zipper{"}, which is constituted by a tight side-chain complementation of the opposing β-sheet layers. In this study, several all-atom molecular dynamics simulations with explicit water were conducted to investigate the importance of steric zipper on the aggregation of the MVGGVV peptide. Our results show that the structural stability of the MVGGVV oligomers increases with increasing the number of β-strands. We further proposed that the octameric structure (the SH2-ST4 model in this study) is the possible nucleus seed for MVGGVV protofibril formation. Our results also demonstrated that hydrophobic interaction is the principle driving force to stabilize the adjacent β-strands while the steric zipper involved M1, V2, V5 and V6 is responsible for holding the neighboring β-sheet layers together. Finally, a twisted model of the MVGGVV assembly (SH2-ST50), based on the averaged twisted angle of ∼ 11.5° between the adjacent β-strands of the SH2-ST4 model, was proposed. Our results gain insights into the aggregation of the MVGGVV peptide in atomic details and may provide a hint for designing new inhibitors able to prevent the fibril formation of the Aβ peptide.",
keywords = "Alzheimer's disease, Amyloid fibril, Amyloid-β, Molecular dynamics (MD) simulation, Parkinson's disease, Peptide, Steric zipper",
author = "Chang, {Liang Kai} and Zhao, {Jian Hua} and Liu, {Hsuan Liang} and Wu, {Josephine W.} and Chuang, {Chih Kuang} and Liu, {Kung Tien} and Chen, {Jenn Tzong} and Tsai, {Wei Bor} and Yih Ho",
year = "2010",
month = "8",
language = "English",
volume = "28",
pages = "39--50",
journal = "Journal of Biomolecular Structure and Dynamics",
issn = "0739-1102",
publisher = "Adenine Press",
number = "1",

}

TY - JOUR

T1 - The importance of steric zipper on the aggregation of the MVGGVV peptide derived from the amyloid β peptide

AU - Chang, Liang Kai

AU - Zhao, Jian Hua

AU - Liu, Hsuan Liang

AU - Wu, Josephine W.

AU - Chuang, Chih Kuang

AU - Liu, Kung Tien

AU - Chen, Jenn Tzong

AU - Tsai, Wei Bor

AU - Ho, Yih

PY - 2010/8

Y1 - 2010/8

N2 - Amyloid-like fibrils are found in many fatal diseases, such as Alzheimer's disease, Parkinson's disease, type II diabetes mellitus, and prion diseases. Recently, the structural characterization of the MVGGVV peptide from the C-terminal hydrophobic segment of the amyloid-β (Aβ) peptide has revealed a general feature of amyloid-like fibrils, termed as "steric zipper", which is constituted by a tight side-chain complementation of the opposing β-sheet layers. In this study, several all-atom molecular dynamics simulations with explicit water were conducted to investigate the importance of steric zipper on the aggregation of the MVGGVV peptide. Our results show that the structural stability of the MVGGVV oligomers increases with increasing the number of β-strands. We further proposed that the octameric structure (the SH2-ST4 model in this study) is the possible nucleus seed for MVGGVV protofibril formation. Our results also demonstrated that hydrophobic interaction is the principle driving force to stabilize the adjacent β-strands while the steric zipper involved M1, V2, V5 and V6 is responsible for holding the neighboring β-sheet layers together. Finally, a twisted model of the MVGGVV assembly (SH2-ST50), based on the averaged twisted angle of ∼ 11.5° between the adjacent β-strands of the SH2-ST4 model, was proposed. Our results gain insights into the aggregation of the MVGGVV peptide in atomic details and may provide a hint for designing new inhibitors able to prevent the fibril formation of the Aβ peptide.

AB - Amyloid-like fibrils are found in many fatal diseases, such as Alzheimer's disease, Parkinson's disease, type II diabetes mellitus, and prion diseases. Recently, the structural characterization of the MVGGVV peptide from the C-terminal hydrophobic segment of the amyloid-β (Aβ) peptide has revealed a general feature of amyloid-like fibrils, termed as "steric zipper", which is constituted by a tight side-chain complementation of the opposing β-sheet layers. In this study, several all-atom molecular dynamics simulations with explicit water were conducted to investigate the importance of steric zipper on the aggregation of the MVGGVV peptide. Our results show that the structural stability of the MVGGVV oligomers increases with increasing the number of β-strands. We further proposed that the octameric structure (the SH2-ST4 model in this study) is the possible nucleus seed for MVGGVV protofibril formation. Our results also demonstrated that hydrophobic interaction is the principle driving force to stabilize the adjacent β-strands while the steric zipper involved M1, V2, V5 and V6 is responsible for holding the neighboring β-sheet layers together. Finally, a twisted model of the MVGGVV assembly (SH2-ST50), based on the averaged twisted angle of ∼ 11.5° between the adjacent β-strands of the SH2-ST4 model, was proposed. Our results gain insights into the aggregation of the MVGGVV peptide in atomic details and may provide a hint for designing new inhibitors able to prevent the fibril formation of the Aβ peptide.

KW - Alzheimer's disease

KW - Amyloid fibril

KW - Amyloid-β

KW - Molecular dynamics (MD) simulation

KW - Parkinson's disease

KW - Peptide

KW - Steric zipper

UR - http://www.scopus.com/inward/record.url?scp=77956544501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956544501&partnerID=8YFLogxK

M3 - Article

C2 - 20476794

AN - SCOPUS:77956544501

VL - 28

SP - 39

EP - 50

JO - Journal of Biomolecular Structure and Dynamics

JF - Journal of Biomolecular Structure and Dynamics

SN - 0739-1102

IS - 1

ER -