| First Author | Buchko GW | Year | 2013 |
| Journal | Arch Biochem Biophys | Volume | 537 |
| Issue | 2 | Pages | 217-24 |
| PubMed ID | 23896516 | Mgi Jnum | J:206681 |
| Mgi Id | MGI:5551683 | Doi | 10.1016/j.abb.2013.07.015 |
| Citation | Buchko GW, et al. (2013) A solution NMR investigation into the impaired self-assembly properties of two murine amelogenins containing the point mutations T21-->I or P41-->T. Arch Biochem Biophys 537(2):217-24 |
| abstractText | Amelogenesis imperfecta describes a group of inherited disorders that results in defective tooth enamel. Two disorders associated with human amelogenesis imperfecta are the point mutations T21-->I or P40-->T in amelogenin, the dominant protein present during the early stages of enamel biomineralization. The biophysical properties of wildtype murine amelogenin (M180) and two proteins containing the equivalent mutations in murine amelogenin, T21-->I (M180-I) and P41-->T (M180-T), were probed by NMR spectroscopy. At low protein concentration (0.1mM), M180, M180-I, and M180-T are predominately monomeric at pH 3.0 in 2% acetic acid and neither mutation produces a major structural change. Chemical shift perturbation studies as a function of protein (0.1-1.8mM) or NaCl (0-400mM) concentrations show that the mutations affect the self-association properties by causing self-assembly at lower protein or salt concentrations, relative to wildtype amelogenin, with the largest effect observed for M180-I. Under both conditions, the premature self-assembly is initiated near the N-terminus, providing further evidence for the importance of this region in the self-assembly process. The self-association of M180-I and M180-T at lower protein concentrations and lower ionic strengths than wildtype M180 may account for the clinical phenotypes of these mutations, defective enamel formation. |
