PMID- 20158453
OWN - NLM
STAT- MEDLINE
DCOM- 20100622
LR  - 20191027
IS  - 1875-5550 (Electronic)
IS  - 1389-2037 (Linking)
VI  - 11
IP  - 2
DP  - 2010 Mar
TI  - Structure of the prion protein and its gene: an analysis using bioinformatics and 
      computer simulation.
PG  - 166-79
AB  - 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.
FAU - Sakudo, Akikazu
AU  - Sakudo A
AD  - Laboratory of Biometabolic Chemistry, School of Health Sciences, Faculty of 
      Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, 
      Japan. sakudo@med.u-ryukyu.ac.jp
FAU - Xue, Guangai
AU  - Xue G
FAU - Kawashita, Norihito
AU  - Kawashita N
FAU - Ano, Yasuhisa
AU  - Ano Y
FAU - Takagi, Tatsuya
AU  - Takagi T
FAU - Shintani, Hideharu
AU  - Shintani H
FAU - Tanaka, Yasuharu
AU  - Tanaka Y
FAU - Onodera, Takashi
AU  - Onodera T
FAU - Ikuta, Kazuyoshi
AU  - Ikuta K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Protein Pept Sci
JT  - Current protein & peptide science
JID - 100960529
RN  - 0 (Prions)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - *Computational Biology
MH  - *Computer Simulation
MH  - Humans
MH  - *Models, Molecular
MH  - Polymorphism, Genetic
MH  - Prion Diseases/genetics
MH  - Prions/*chemistry/*genetics
RF  - 81
EDAT- 2010/02/18 06:00
MHDA- 2010/06/23 06:00
CRDT- 2010/02/18 06:00
PHST- 2008/12/29 00:00 [received]
PHST- 2009/08/01 00:00 [accepted]
PHST- 2010/02/18 06:00 [entrez]
PHST- 2010/02/18 06:00 [pubmed]
PHST- 2010/06/23 06:00 [medline]
AID - CPPS-39 [pii]
AID - 10.2174/138920310790848386 [doi]
PST - ppublish
SO  - Curr Protein Pept Sci. 2010 Mar;11(2):166-79. doi: 10.2174/138920310790848386.