| First Author | Lysek DA | Year | 2004 |
| Journal | Biochemistry | Volume | 43 |
| Issue | 32 | Pages | 10393-9 |
| PubMed ID | 15301538 | Mgi Jnum | J:201317 |
| Mgi Id | MGI:5512962 | Doi | 10.1021/bi0494828 |
| Citation | Lysek DA, et al. (2004) Prion protein interaction with the C-terminal SH3 domain of Grb2 studied using NMR and optical spectroscopy. Biochemistry 43(32):10393-9 |
| abstractText | Transmissible spongiform encephalopathies have been observed exclusively in organisms expressing the host-encoded prion protein (PrP). The function of the cellular isoform of PrP found in healthy organisms has so far not been identified, although there are indications of a role in signal transduction in neurons. To gain further insight into the functional properties of cellular PrP, this paper investigated the binding of the C-terminal SH3 domain of the murine growth factor receptor-bound protein 2 (Grb2) to the murine PrP, using NMR, fluorescence, and circular dichroism spectroscopy. The SH3-binding site in murine PrP was thus found to be in the highly conserved region of residues 100-109, which contains prolines in positions 101 and 104. The protein-protein interaction, with a K(D) value of 5.5 microM, is abolished when either of these two prolines is replaced by leucine. In humans, two corresponding Pro --> Leu exchanges are found in patients who present with the Gerstmann-Straussler-Scheinker syndrome. The results of the present study thus indicate a possible mechanism by which amino acid exchanges could influence a specific protein-protein interaction in a complex signal transduction cascade, which might be of functional significance in health and disease. |
