Structure of the Prion Protein and Its Gene: An Analysis Using Bioinformatics and Computer Simulation

Title: Structure of the Prion Protein and Its Gene: An Analysis Using Bioinformatics and Computer Simulation

Volume: 11 Issue: 2

Author(s): Akikazu Sakudo, Guangai Xue, Norihito Kawashita, Yasuhisa Ano, Tatsuya Takagi, Hideharu Shintani, Yasuharu Tanaka, Takashi Onodera and Kazuyoshi Ikuta

Affiliation:

Keywords: Prion protein gene, polymorphism, bovine spongiform encephalopathy, prion, molecular dynamics (MD), quantum mechanics (QM)

Abstract: Prion protein (PrP) gene encodes cellular PrP (PrPC), a glycosylphosphatidylinositol (GPI)-anchored cell membrane protein indispensable for infections of prion, which causes Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep. Although PrPC is known to be converted into an abnormal isoform (PrPSc) upon prion infection and play an important role in prion diseases, the mechanisms involved remain unclear, partly due to the insolubility of PrPSc, which prevents experimental biochemical and biophysical analyses. Recently, with improvements in computer power and methods, computer analyses have been contributing more to prion studies. A comparison of PrP gene sequences revealed mutations and polymorphisms in the open reading frame (ORF) of the human PrP gene related to prion diseases. In contrast, little mutations or polymorphisms related to susceptibility to BSE were found in the ORF of the bovine PrP gene, though relationships between insertion/deletion (Ins/Del) polymorphisms of the PrP gene promoter and susceptibility to BSE have been found. Our results have shown that the specific protein 1 (Sp1) plays important role in the activity of PrP gene promoter, which is influenced by polymorphisms in the Sp1 binding sites. The potential structural dynamics of PrP have been simulated by computational methods such as molecular dynamics (MD) and quantum mechanics (QM). The proposed mechanisms of conversion have revealed new insights in prion diseases. In this review, we will introduce the gene structure, polymorphisms, and potential structural dynamics of PrP revealed by basic and advanced computational analyses. The possible contribution of these methods to elucidation of the pathogenicity of prion diseases and functions of PrPC is discussed.

Cite this article as:

Sakudo Akikazu, Xue Guangai, Kawashita Norihito, Ano Yasuhisa, Takagi Tatsuya, Shintani Hideharu, Tanaka Yasuharu, Onodera Takashi and Ikuta Kazuyoshi, Structure of the Prion Protein and Its Gene: An Analysis Using Bioinformatics and Computer Simulation, Current Protein & Peptide Science 2010; 11 (2) . https://dx.doi.org/10.2174/138920310790848386

DOI https://dx.doi.org/10.2174/138920310790848386	Print ISSN 1389-2037
Publisher Name Bentham Science Publisher	Online ISSN 1875-5550