Enamel biomineralization: Solution- and solid-state NMR studies of a natural protein-mineral interfaces
EMSL Project ID
44691
Abstract
Dental enamel, the 1-2 mm layer of elongated carbonated hydroxayapatite on the outer layer of the tooth, is the hardest tissue in the human body. It needs to be strong because it is exposed to repeated masticatory, parafunctional, and occasional impact loading, but unlike the dominant biomineral in the human body, our bones, enamel cannot self-repair nor can it undergo remodeling. Therefore, enamel must last a lifetime. Enamel's resistance to wear and deformation are due to a combination of high mineral content and unique three-dimensional structural organization. Ninety-five percent of mature enamel consists of long and narrow crystals of carbonated hydroxyapatite packed into parallel arrays, called enamel rods or prisms, that are intricately interwoven into an unique lattice. There is little, if any, matrix protein remaining in mature enamel, another feature differentiating enamel markedly from dentin and bone. The nucleation, growth, and organization of enamel (amelogenesis) are extracellular processes orchestrated by one predominant enamel matrix protein, amelogenin, that is secreted by the inner enamel epithelium (ameloblasts) and found exclusively in the region of newly formed enamel. Specific mutations to amelogenin and amelogenin deficient mice both result in dramatic enamel phenotypes similar to amelogenesis imperfecta in humans, observations that strongly suggest amelogenin plays an essential role in amelogenesis. Of the many interesting features of amelogenin perhaps the most remarkable is its ability, under the correct conditions, to self-assemble into a unique quaternary structure, termed 'nanosphere', that appears to be an essential functional and structural component of the secretory-stage enamel matrix. While it is clear that amelogenin plays an essential role in enamel formation, its functional role is largely unknown. Elucidating the molecular level mechanisms driving enamel formation may have immediate applications towards repairing damaged or deficient enamel and a broader application as a model for understanding protein-mediated biomineralization processes in nature.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2011-12-14
End Date
2012-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Buchko GW, G Lin, BJ Tarasevich, and WJ Shaw. 2013. "A solution NMR investigation into the impaired self-assembly properties of two murine amelogenins containing the point mutations T21?I or P41?T." Archives of Biochemistry and Biophysics 537(2):217-224. doi:10.1016/j.abb.2013.07.015
G.W. Buchko and W.J. Shaw (2015) Improved protocol to purify untagged amelogenin - Application to murine amelogenin containing the equivalent P70&8594T point mutation observed in human amelogenesis imperfecta. Protein Expr. Purif.. 105:14-22.
Lu J, Y Xu, GW Buchko, and WJ Shaw. 2013. "Mineral Association Changes the Secondary Structure and Dynamics of Murine Amelogenin." Journal of Dental Research 92(11):1000-1004. doi:10.1177/0022034513504929
Tao J, GW Buchko, WJ Shaw, J De Yoreo, and BJ Tarasevich. 2015. "Sequence-defined Energetic Shifts Control the Disassembly Kinetics and Microstructure of Amelogenin Adsorbed onto Hydroxyapatite (100)." Langmuir 31(38):10451-10460. doi:10.1021/acs.langmuir.5b02549
Tarasevich BJ, JS Philo, NK Maluf, S Krueger, GW Buchko, G Lin, and WJ Shaw. 2015. "The Leucine-Rich Amelogenin Protein (LRAP) is primarily monomeric and unstructured in physiological solution." Journal of Structural Biology 190(1):81-91. doi:10.1016/j.jsb.2014.10.007