| First Author | Thaa B | Year | 2008 |
| Journal | Biochim Biophys Acta | Volume | 1783 |
| Issue | 6 | Pages | 1076-84 |
| PubMed ID | 18088603 | Mgi Jnum | J:136757 |
| Mgi Id | MGI:3796940 | Doi | 10.1016/j.bbamcr.2007.11.007 |
| Citation | Thaa B, et al. (2008) The deletion of amino acids 114-121 in the TM1 domain of mouse prion protein stabilizes its conformation but does not affect the overall structure. Biochim Biophys Acta 1783(6):1076-84 |
| abstractText | A mutant of mouse prion protein (PrPC) carrying a deletion of residues 114-121 (PrPDelta114-121) has previously been described to lack convertibility into the scrapie-associated isoform of PrP (PrPSc) and to exhibit a dominant-negative effect on the conversion of wild-type PrPC into PrPSc in living cells. Here we report the characterization of recombinantly expressed PrPDelta114-121 by Fourier-transformation infrared spectroscopy (FTIR) and circular dichroism (CD) spectroscopy. The analysis of spectra revealed an increased antiparallel beta-sheet content in the deletion mutant compared to wild-type PrPC. This additional short beta-sheet stabilized the fold of the mutant protein by DeltaDeltaG(0)'=3.4+/-0.3 kJ mol(-1) as shown by chemical unfolding experiments using guanidine hydrochloride. Secondary structure predictions suggest that the additional beta-sheet in PrPDelta114-121 is close to the antiparallel beta-sheet in PrPC. The high-affinity Cu2+-binding site outside the octarepeats, which is located close to the deletion and involves His110 as a ligand, was not affected, as detected by electron paramagnetic resonance (EPR) spectroscopy, suggesting that Cu2+ binding does not contribute to the protection of PrPDelta114-121 from conversion into PrPSc. We propose that the deletion of residues 114-121 stabilizes the mutant protein. This stabilization most likely does not obstruct the interaction of PrPDelta114-121 with PrPSc but represents an energy barrier that blocks the conversion of PrPDelta114-121 into PrPSc. |
