The tooth enamel protein, porcine amelogenin, is an intrinsically disordered protein with an extended molecular configuration in the monomeric form

Katya Delak, Craig Harcup, Rajamani Lakshminarayanan, Zhi Sun, Yuwwei Fan, Janet Moradian-Oldak, John Evans

Research output: Contribution to journalArticle

Abstract

Amelogenins make up a class of proteins associated with the formation of mineralized enamel in vertebrates, possess highly conserved N- and C-terminal sequence regions, and represent an interesting model protein system for understanding biomineralization and protein assembly. Using bioinformatics, we report here the identification of molecular traits that classify 12 amelogenin proteins as members of the intrinsically disordered or unstructured protein family (IDPs), a group of proteins that normally exist as unfolded species but are capable of transformation to a folded state as part of their overall function. Using biophysical techniques (CD and NMR), we follow up on our bioinformatics studies and confirm that one of the amelogenins, recombinant porcine rP172, exists in an extended, unfolded state in the monomeric form. This protein exhibits evidence of conformational exchange between two states, and this exchange may be mediated by Pro residues in the sequence. Although the protein is globally unfolded, we detect the presence of local residual secondary structure [α-helix, extended β-strand, turn/loop, and polyproline type II (PPII)] that may serve several functional roles within the enamel matrix. The extended, labile conformation of rP172 amelogenin is compatible with the known functions of amelogenin in enamel biomineralization, i.e., self-assembly, associations with other enamel matrix proteins and with calcium phosphate biominerals, and interaction with cell receptors. It is likely that the labile structure of this protein facilitates interactions of amelogenin with other macromolecules or with minerals for achievement of internal protein stabilization.

Original languageEnglish (US)
Pages (from-to)2272-2281
Number of pages10
JournalBiochemistry
Volume48
Issue number10
DOIs
StatePublished - Mar 17 2009

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Tooth enamel
Intrinsically Disordered Proteins
Amelogenin
Molecular Conformation
Dental Enamel
Tooth
Swine
Proteins
Enamels
Biomineralization
Bioinformatics
Computational Biology
Inosine Diphosphate
Macromolecules
Cell Communication
Self assembly
Minerals
Conformations
Vertebrates
Stabilization

ASJC Scopus subject areas

  • Biochemistry

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The tooth enamel protein, porcine amelogenin, is an intrinsically disordered protein with an extended molecular configuration in the monomeric form. / Delak, Katya; Harcup, Craig; Lakshminarayanan, Rajamani; Sun, Zhi; Fan, Yuwwei; Moradian-Oldak, Janet; Evans, John.

In: Biochemistry, Vol. 48, No. 10, 17.03.2009, p. 2272-2281.

Research output: Contribution to journalArticle

Delak, Katya ; Harcup, Craig ; Lakshminarayanan, Rajamani ; Sun, Zhi ; Fan, Yuwwei ; Moradian-Oldak, Janet ; Evans, John. / The tooth enamel protein, porcine amelogenin, is an intrinsically disordered protein with an extended molecular configuration in the monomeric form. In: Biochemistry. 2009 ; Vol. 48, No. 10. pp. 2272-2281.
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