Binding of recombinant but not endogenous prion protein to DNA Causes DNA internalization and expression in mammalian cells

Shaoman Yin, Xingjun Fan, Shuiliang Yu, Chaoyang Li, Man Sun Sy

Research output: Contribution to journalArticle

17 Scopus citations


Recombinant prion protein, rPrP, binds DNA. Both the KKRPK motif and the octapeptide repeat region of rPrP are essential for maximal binding. rPrP with pathogenic insertional mutations binds more DNA than wild-type rPrP. DNA promotes the aggregation of rPrP and protects its N terminus from proteinase K digestion. When rPrP is mixed with an expression plasmid and Ca2+, the rPrP·DNA complex is taken up by mammalian cells leading to gene expression. In the presence of Ca2+, rPrP by itself is also taken up by cells in a temperature- and pinocytosis-dependent manner. Cells do not take up rPrPΔKKRPK, which lacks the KKRPK motif. Thus, rPrP is the carrier for DNA and the KKRPK motif is essential for its uptake. When mixed with DNA, a pentapeptide KKRPK, but not KKKKK, is sufficient for DNA internalization and expression. In contrast, whereas the normal cellular prion protein, PrPC, on the cell surface can also internalize DNA, the imported DNA is not expressed. These findings may have relevance to the normal functions of PrPC and the pathogenic mechanisms of human prion disease.

Original languageEnglish (US)
Pages (from-to)25446-25454
Number of pages9
JournalJournal of Biological Chemistry
Issue number37
Publication statusPublished - Sep 12 2008
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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