The Structural Biology of the Developing Dental Enamel Matrix

Fincham, Alan G.; Moradian‐Oldak, Janet; Simmer, James P.

doi:10.1006/jsbi.1999.4130

Cited by 553 publications

(578 citation statements)

References 212 publications

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“…[1][2][3] The major protein component, amelogenin, is essential for normal enamel development and forms supramolecular assemblies (nanospheres) 4,5 that are believed to exert control over the mineral phase, morphology, organization, and directionality of hydroxyapatite crystal growth. 6,7 Recent bioinformatics and biophysical studies 8,9 have demonstrated that several amelogenins have sequence characteristics that fit the profile of intrinsically disordered proteins or IDPs.…”

Section: Introductionmentioning

confidence: 99%

“…27 It is experimentally challenging to assess the folding propensities of the three major regions of porcine amelogenin in the presence of matrix targets or during the self-assembly process. One of the major reasons for this is that the enamel matrix is a complex environment [2][3][4][5][6][20][21][22][23][24][25] and the true identity of amelogenin-specific targets, solution conditions, and other important features are not known at present. The other reason is that the amelogenin oligomerization process itself is quite complex 5,15,18,[20][21][22][23]27 and results in the formation of high-order high-molecular weight complexes that are difficult to study with conventional structural techniques such as NMR.…”

Section: Introductionmentioning

confidence: 99%

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Probing the self‐association, intermolecular contacts, and folding propensity of amelogenin

et al. 2011

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Amelogenins are an intrinsically disordered protein family that plays a major role in the development of tooth enamel, one of the most highly mineralized materials in nature. Monomeric porcine amelogenin possesses random coil and residual secondary structures, but it is not known which sequence regions would be conformationally attractive to potential enamel matrix targets such as other amelogenins (self-assembly), other matrix proteins, cell surfaces, or biominerals. To address this further, we investigated recombinant porcine amelogenin (rP172) using ''solvent engineering'' techniques to simultaneously promote native-like structure and induce amelogenin oligomerization in a manner that allows identification of intermolecular contacts between amelogenin molecules. We discovered that in the presence of 2,2,2-trifluoroethanol (TFE) significant folding transitions and stabilization occurred primarily within the N-and C-termini, while the polyproline Type II central domain was largely resistant to conformational transitions. Seven Pro residues (P2, P127, P130, P139, P154, P157, P162) exhibited conformational response to TFE, and this indicates these Pro residues act as folding enhancers in rP172. The remaining Pro residues resisted TFE perturbations and thus act as conformational stabilizers. We also noted that TFE induced rP172 self-association via the formation of intermolecular contacts involving P4-H6, V19-P33, and E40-T58 regions of the N-terminus. Collectively, these results confirm that the Nand C-termini of amelogenin are conformationally responsive and represent potential interactive sites for amelogenin-target interactions during enamel matrix mineralization. Conversely, the Pro, Gln central domain is resistant to folding and this may have important functional significance for amelogenin.Abbreviations: AQ-rP172, uniformly labeled 13 C, 15 N rP172 in 90% v/v UDDW, 10% v/v D 2 O, pH 3.8; CD, circular dichroism; DLS, dynamic light scattering; HSQC, heteronuclear single quantum coherence; IDP, intrinsically disordered protein; rP172, recombinant porcine amelogenin; 70-rP172, uniformly labeled 13 C, 15 N rP172 in 30% v/v UDDW, 70% v/v 2,2,2-trifluoroethanol, pH 3.8; RC, random coil; SSP, secondary structure propensity score; TFE, 2,2,2-trifluoroethanol; UDDW, Milli-Q pure unbuffered deionized distilled water.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Probing the self‐association, intermolecular contacts, and folding propensity of amelogenin

et al. 2011

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“…Enamel is an example of a biomineral system with a nucleation mechanism that is not well understood. Enamel is one of the most highly ordered biominerals, composed of elongated hydroxyapatite crystals assembled into prisms [2]. Unlike bone, enamel does not have a structural matrix like collagen and it is not remodeled.…”

Section: Introductionmentioning

confidence: 99%

“…Amelogenin, a hydrophobic protein with most of the charged amino acids located in the Nand C-termini, constitutes 90% of the protein present during enamel formation [2]. In spite of its prominence in developing enamel, the function of amelogenin is not completely understood.…”

Section: Introductionmentioning

confidence: 99%

The nucleation and growth of calcium phosphate by amelogenin

Tarasevich

Howard

Larson

et al. 2007

Journal of Crystal Growth

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The nucleation processes involved in calcium phosphate formation in tooth enamel are not well understood but are believed to involve proteins in the extracellular matrix. The ability of one enamel protein, amelogenin, to promote the nucleation and growth of calcium phosphate was studied in an in vitro system involving metastable supersaturated solutions. It was found that recombinant amelogenin (rM179 and rp(H)M180) promoted the nucleation of calcium phosphate compared to solutions without protein. The amount of calcium phosphate increased with increasing supersaturation of the solutions and increasing protein concentrations up to 6.5 μg/mL. At higher protein concentrations, the amount of calcium phosphate decreased. The kinetics of nucleation was studied in situ and in real time using a quartz crystal microbalance (QCM) and showed that the protein reduced the induction time for nucleation compared to solutions without protein. This work shows a nucleation role for amelogenin in vitro which may be promoted by the association of amelogenin into nanosphere templates, exposing charged functionality at the surface.

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“…They comprise 90% of the developing extracellular enamel matrix proteins (Termine et al, 1980) and play a major role in the biomineralization and structural organization of enamel (Robinson et al, 1998;Fincham et al, 1999). Amelogenins are hydrophobic molecules that self-assemble in vitro and in vivo into nanospheric structures, which regulate the oriented and elongated growth, shape, and size of the enamel mineral crystal (Fincham et al, 1994;Du et al, 2005).…”

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confidence: 99%

Amelogenin expression in long bone and cartilage cells and in bone marrow progenitor cells

Haze

Taylor

Blumenfeld

et al. 2007

The Anatomical Record

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The amelogenin protein is considered as the major molecular marker of developing ectodermal enamel. Recent data suggest other roles for amelogenin beyond structural regulation of enamel mineral crystal growth. Here we describe our novel discovery of amelogenin expression in long bone cells, in cartilage cells, in cells of the epiphyseal growth plate, and in bone marrow stromal cells. Anat Rec, 290:455-460, 2007. 2007 Wiley-Liss, Inc.

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The Structural Biology of the Developing Dental Enamel Matrix

Cited by 553 publications

References 212 publications

Probing the self‐association, intermolecular contacts, and folding propensity of amelogenin

Probing the self‐association, intermolecular contacts, and folding propensity of amelogenin

The nucleation and growth of calcium phosphate by amelogenin

Amelogenin expression in long bone and cartilage cells and in bone marrow progenitor cells

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