Interrogating the Dimerization Interface of the Prion Protein Via Site-Specific Mutations to p-Benzoyl-L-Phenylalanine

Sudheer Babu Sangeetham, Krisztina Huszár, Petra Bencsura, Antal Nyeste, Éva Hunyadi-Gulyás, Elfrieda Fodor, Ervin Welker

Research output: Contribution to journalArticle

1 Citation (Scopus)


Transmissible spongiform encephalopathies are centered on the conformational transition of the prion protein from a mainly helical, monomeric structure to a β-sheet rich ordered aggregate. Experiments indicate that the main infectious and toxic species in this process are however shorter oligomers, formation of which from the monomers is yet enigmatic. Here, we created 25 variants of the mouse prion protein site-specifically containing one genetically-incorporated para-benzoyl-phenylalanine (pBpa), a cross-linkable non-natural amino acid, in order to interrogate the interface of a prion protein-dimer, which might lie on the pathway of oligomerization. Our results reveal that the N-terminal part of the prion protein, especially regions around position 127 and 107, is integral part of the dimer interface. These together with additional pBpa-containing variants of mPrP might also facilitate to gain more structural insights into oligomeric and fibrillar prion protein species including the pathological variants.

Original languageEnglish
Pages (from-to)2784-2801
Number of pages18
JournalJournal of molecular biology
Issue number17
Publication statusPublished - Aug 17 2018


  • Dimerization
  • Photo-crosslinking
  • Prion
  • Protein conformational stability
  • pBpa

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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