Investigation of the effect of glycosylation on human prion protein by molecular dynamics

Linghao Zhong, Jimin Xie

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Prion protein conformational isomerization, PrPc→PrPSc, has been attributed as the cause of TSE diseases such as mad-cow disease. The mechanism of such isomerization, however, is little known due the experimental difficulties in studying the scrapie form. Among factors that affect PrP isomerization, the role which glycosylation plays remains vague. The number of innumerous glycan species, together with their high flexibility, leads to ineffective structural characterization. In this research, we studied the effect of chitobiose glycosylation on human PrP, in both monomeric (huPrPmono) and dimeric (huPrPdimer) forms, by molecular dynamics (MD) simulations. Our results show that this glycosylation has minimal impact on the structure of huPrPmono. However, it affects the secondary structure of dimeric protein. An additional β-sheet strand is found while the glycosylation is absent in the huPrPdimer. Comparatively, when the protein is glycosylated with chitobiose, such β-sheet addition is not observed.

Original languageEnglish (US)
Pages (from-to)525-533
Number of pages9
JournalJournal of Biomolecular Structure and Dynamics
Volume26
Issue number5
DOIs
StatePublished - Jan 1 2009

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Molecular Dynamics Simulation
Glycosylation
Bovine Spongiform Encephalopathy
Secondary Protein Structure
Scrapie
Polysaccharides
Prion Proteins
Research
Proteins
chitobiose

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

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abstract = "Prion protein conformational isomerization, PrPc→PrPSc, has been attributed as the cause of TSE diseases such as mad-cow disease. The mechanism of such isomerization, however, is little known due the experimental difficulties in studying the scrapie form. Among factors that affect PrP isomerization, the role which glycosylation plays remains vague. The number of innumerous glycan species, together with their high flexibility, leads to ineffective structural characterization. In this research, we studied the effect of chitobiose glycosylation on human PrP, in both monomeric (huPrPmono) and dimeric (huPrPdimer) forms, by molecular dynamics (MD) simulations. Our results show that this glycosylation has minimal impact on the structure of huPrPmono. However, it affects the secondary structure of dimeric protein. An additional β-sheet strand is found while the glycosylation is absent in the huPrPdimer. Comparatively, when the protein is glycosylated with chitobiose, such β-sheet addition is not observed.",
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Investigation of the effect of glycosylation on human prion protein by molecular dynamics. / Zhong, Linghao; Xie, Jimin.

In: Journal of Biomolecular Structure and Dynamics, Vol. 26, No. 5, 01.01.2009, p. 525-533.

Research output: Contribution to journalArticle

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AU - Xie, Jimin

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