Synthetic human prion protein octapeptide repeat binds to the proteinase K active site

Dessislava Georgieva, Wojciech Rypniewski, Hartmut Echner, Markus Perbandt, Mirjam Koker, Joachim Clos, Lars Redecke, Reinhard Bredehorst, Wolfgang Voelter, Nicolay Genov, Christian Betzel

8 Citations (Scopus)


Proteinase K is widely used in tests for the presence of infectious prion protein causing fatal spongiform encephalopathies. To investigate possible interactions between the enzyme and the functionally important N-terminal prion domain, we crystallized mercury-inhibited proteinase K in the presence of the synthetic peptides GGGWGQPH and HGGGW. The octapeptide sequence is identical to that of a single octapeptide repeat (OPR) from the physiologically important OPR region. Here, we present the first direct evidence for the complex formation between a proteolytic enzyme and a segment of human prion molecule. The X-ray structures of the complexes at 1.4 and 1.8 Å resolution, respectively, revealed that in both cases the segment GGG is strongly bound as a real substrate at the substrate recognition site of the proteinase forming an antiparallel β-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Issue number4
Pages (from-to)1406-1411
Number of pages6
Publication statusPublished - 24.12.2004

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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