Elongated Polyproline Motifs Facilitate Enamel Evolution through Matrix Subunit Compaction

Jin, Tianquan; Ito, Yoshihiro; Dangaria, Smit; Walker, Cameron; Allen, Michael J.; Kulkarni, Ashok B.; Gibson, Carolyn W.; Braatz, Richard D.; Liao, Xiubei; Diekwisch, Thomas G.H.

doi:10.1371/journal.pbio.1000262

Cited by 47 publications

(71 citation statements)

References 46 publications

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“…This protein contains a central domain composed of proline-rich tripeptide TRs (PXX). The proline-rich domain adopts a flexible but well-defined helical conformation, which is central to its role as a structural matrix (54). Analysis of amelogenin orthologs shows that the number of repeats increases from amphibians to mammals.…”

Section: Tandem Repeats Mediate Evolvability In Organismal Morphologymentioning

confidence: 99%

Variable Tandem Repeats Accelerate Evolution of Coding and Regulatory Sequences

et al. 2010

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Genotype-to-phenotype mapping commonly focuses on two major classes of mutations: single nucleotide polymorphisms (SNPs) and copy number variation (CNV). Here, we discuss an underestimated third class of genotypic variation: changes in microsatellite and minisatellite repeats. Such tandem repeats (TRs) are ubiquitous, unstable genomic elements that have historically been designated as nonfunctional "junk DNA" and are therefore mostly ignored in comparative genomics. However, as many as 10% to 20% of eukaryotic genes and promoters contain an unstable repeat tract. Mutations in these repeats often have fascinating phenotypic consequences. For example, changes in unstable repeats located in or near human genes can lead to neurodegenerative diseases such as Huntington disease. Apart from their role in disease, variable repeats also confer useful phenotypic variability, including cell surface variability, plasticity in skeletal morphology, and tuning of the circadian rhythm. As such, TRs combine characteristics of genetic and epigenetic changes that may facilitate organismal evolvability.

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Section: Tandem Repeats Mediate Evolvability In Organismal Morphologymentioning

confidence: 99%

Variable Tandem Repeats Accelerate Evolution of Coding and Regulatory Sequences

et al. 2010

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“…After extracellular self-assembly this protein acts both as an extracellular matrix structure, similarly to type I collagen in bone and dentin, for the growing crystallites and a direct interaction partner of hydroxyapatite orienting apatite crystal growth by inhibiting it on a-and b-axis surfaces while promoting apatite crystal growth in c-axis direction [23,24]. This multiple functionality is mainly achieved by PXX amino acid triplet repeats [26]. The uniqueness of amelogenesis derives from the tight junction forming capacity of ameloblasts that isolate apical and basolateral surfaces separating the space of enamel mineralization from the interstitial compartment [7,27], which eliminates the need of large quantities of special phosphoproteins necessary for bone and dentin mineralization [14].…”

Section: Significance Of Intrinsically Disordered Proteins Involved Imentioning

confidence: 99%

Function and repair of dental enamel – Potential role of epithelial transport processes of ameloblasts

et al. 2015

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“…[9][10][11][12][13][14] The existence of unstructured regions within monomeric amelogenin have been confirmed by solution NMR studies of two recombinant amelogenins, murine 15 and porcine, 9 as well as model peptides representing amelogenin polyproline Type II (PPII) repeat regions. 16 In the case of the porcine species, under low pH aqueous conditions the monomeric form of amelogenin exists in an extended, unfolded state. 9 It is suspected that intrinsic disorder contributes to the structure and function of these proteins in self-assembly 5,9,15,[17][18][19][20][21][22] and in cellmatrix, protein-matrix, and protein-mineral interactions.…”

Section: Introductionmentioning

confidence: 99%

“…Recent NMR studies of recombinant porcine amelogenin (rP172) indicated that there are three primary regions that are structurally distinct. 9 These are the highly conserved N-terminus (P2-W45) 26 or the proposed selfassembly ''A domain'' (P2-M42), [20][21][22] the partially condensed, charged C-terminal domain (D155-D173), 9,[20][21][22] and the extended Pro, Met, Gln-rich central domain (T58-P154) 9,16 that contains the polyproline Type II I70-P89 and P102-P145 sequence regions. 9 Both terminal domains exhibited evidence of residual secondary structure, 9 and these terminal regions may represent putative regions for folding during amelogenin-target interactions or self-assembly.…”

Section: Introductionmentioning

confidence: 99%

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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Elongated Polyproline Motifs Facilitate Enamel Evolution through Matrix Subunit Compaction

Cited by 47 publications

References 46 publications

Variable Tandem Repeats Accelerate Evolution of Coding and Regulatory Sequences

Variable Tandem Repeats Accelerate Evolution of Coding and Regulatory Sequences

Function and repair of dental enamel – Potential role of epithelial transport processes of ameloblasts

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

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