title: Amyloid-like ribbons of amelogenins in enamel mineralization.
abstract: Enamel, the outermost layer of teeth, is an acellular mineralized tissue that cannot regenerate; the mature tissue is composed of high aspect ratio apatite nanocrystals organized into rods and inter-rod regions. Amelogenin constitutes 90% of the protein matrix in developing enamel and plays a central role in guiding the hierarchical organization of apatite crystals observed in mature enamel. To date, a convincing link between amelogenin supramolecular structures and mature enamel has yet to be described, in part because the protein matrix is degraded during tissue maturation. Here we show compelling evidence that amelogenin self-assembles into an amyloid-like structure in vitro and in vivo. We show that enamel matrices stain positive for amyloids and we identify a specific region within amelogenin that self-assembles into β-sheets. We propose that amelogenin nanoribbons template the growth of apatite mineral in human enamel. This is a paradigm shift from the current model of enamel development.
authors.affiliation: Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Karina M M
authors.initials: KM
authors.lastname: Carneiro
authors.affiliation: Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Halei
authors.initials: H
authors.lastname: Zhai
authors.affiliation: Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.|Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco, CA 94158, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Horst
authors.affiliation: Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Melody
authors.initials: M
authors.lastname: Sitlin
authors.affiliation: Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Mychi
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: Bruker Nano Surfaces Division, 112 Robin Hill Road, Santa Barbara, CA 93117, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Simpliciano
authors.affiliation: Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Milder
authors.affiliation: The Molecular Foundry, Lawrence Berkeley National Laboratory, One Cyclotron Road, Building 67, Berkeley, CA 94720, USA.
authors.forename: Chun-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Pacific Northwest National Laboratory, PO Box 999, MSIN: K4-18, Richland, WA 99352, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Ashby
authors.affiliation: Division of Pure and Applied Biochemistry, Center for Applied Life Sciences, Lund University, P.O. Box 124, SE-221 00, Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Bonde
authors.affiliation: Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Habelitz
mesh_terms: D053523:Amelogenin / Q000737:chemistry* / Q000378:metabolism*; D058227:Amyloidogenic Proteins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003743:Dental Enamel / Q000378:metabolism; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D053523:Amelogenin; D058227:Amyloidogenic Proteins; D007610:Kallikreins; C120801:kallikrein 4