Abstract
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 language | English |
|---|---|
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 325 |
| Issue number | 4 |
| Pages (from-to) | 1406-1411 |
| Number of pages | 6 |
| ISSN | 0006-291X |
| DOIs | |
| Publication status | Published - 24.12.2004 |
Funding
The authors thank the Deutsche Luft- und Raumfahrtagentur (DLR, Projektträger Gesundheitsforschung, Grant 01KO0206) and the RiNA GmbH Berlin for financial support. This work was supported in part by the Bulgarian National Foundation for Scientific Research, Grant X-1301. Ch. Betzel thanks the Deutsche Forschungsgemeinschaft for the financial support during a visit at the Institute of Organic Chemistry, Bulgarian Academy of Sciences, under contract 436 BUL 113/115/8-1.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
