title: The tooth enamel protein, porcine amelogenin, is an intrinsically disordered protein with an extended molecular configuration in the monomeric form.
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 [alpha-helix, extended beta-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.
authors.affiliation: Laboratory for Chemical Physics, New York University, 345 East 24th Street, Room 1007, New York, New York 10010, USA.
authors.forename: Katya
authors.initials: K
authors.lastname: Delak
authors.forename: Craig
authors.initials: C
authors.lastname: Harcup
authors.forename: Rajamani
authors.initials: R
authors.lastname: Lakshminarayanan
authors.forename: Zhi
authors.initials: Z
authors.lastname: Sun
authors.forename: Yuwwei
authors.initials: Y
authors.lastname: Fan
authors.forename: Janet
authors.initials: J
authors.lastname: Moradian-Oldak
authors.forename: John Spencer
authors.initials: JS
authors.lastname: Evans
mesh_terms: D053523:Amelogenin / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D044367:Phase Transition; D011487:Protein Conformation; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012542:Scattering, Radiation; D020539:Sequence Analysis, Protein; D012995:Solubility; D055672:Static Electricity; D013552:Swine; D014867:Water / Q000737:chemistry
chemical_list: D053523:Amelogenin; D011994:Recombinant Proteins; D014867:Water