[NMR paper] A solution NMR investigation into the impaired self-assembly properties of two murine amelogenins containing the point mutations T21->I or P41->T.

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A solution NMR investigation into the impaired self-assembly properties of two murine amelogenins containing the point mutations T21->I or P41->T.

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. 2013 Jul 26;

Authors: Buchko GW, Lin G, Tarasevich BJ, Shaw WJ

Abstract
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 in ameloblasts 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 (0.1 mM) 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 to 1.8 mM) and NaCl (0 to 400 mM) concentration 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.


PMID: 23896516 [PubMed - as supplied by publisher]



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