title: Enamel proteases reduce amelogenin-apatite binding.
abstract: Organic matrix degradation and crystal maturation are extracellular events that occur simultaneously during enamel biomineralization. We hypothesized that enamel proteases control amelogenin-mineral interaction, which, in turn can affect crystal nucleation, organization, and growth. We used a recombinant amelogenin (rP172), a homolog of its major cleavage product (rP148), and a native amelogenin lacking both N- and C-termini (13k). We compared apatite binding affinity between amelogenins and their digest products during proteolysis. We further compared binding affinity among the 3 amelogenins using a Langmuir model for protein adsorption. Amelogenin-apatite binding affinity was progressively reduced with the proteolysis at the C- and N- termini by recombinant pig MMP-20 (rpMMP20) and recombinant human kallikrein-4 (rhKLK4), respectively. The binding affinity of amelogenin to apatite was found to be in the descending order of rP172, rP148, and 13k. Analysis of our data suggests that, before its complete degradation during enamel maturation, stepwise processing of amelogenin by MMP-20 and then KLK4 reduces amelogenin-apatite interaction.
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California, School of Dentistry, 2250 Alcazar St., Los Angeles, CA 90033, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.forename: D
authors.initials: D
authors.lastname: Fan
authors.forename: Y
authors.initials: Y
authors.lastname: Fan
authors.forename: C
authors.initials: C
authors.lastname: Du
authors.forename: J
authors.initials: J
authors.lastname: Moradian-Oldak
mesh_terms: D000327:Adsorption; D000566:Amelogenesis / Q000502:physiology; D053523:Amelogenin / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001031:Apatites / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003743:Dental Enamel / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007610:Kallikreins / Q000494:pharmacology; D053519:Matrix Metalloproteinase 20 / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins; D013552:Swine; D014074:Tooth Calcification / Q000502:physiology
chemical_list: D053523:Amelogenin; D001031:Apatites; D007527:Isoenzymes; D011994:Recombinant Proteins; D010447:Peptide Hydrolases; D007610:Kallikreins; C120801:kallikrein 4; D053519:Matrix Metalloproteinase 20