title: Determination of protein regions responsible for interactions of amelogenin with CD63 and LAMP1.
abstract: The enamel matrix protein amelogenin is secreted by ameloblasts into the extracellular space to guide the formation of highly ordered hydroxyapatite mineral crystallites, and, subsequently, is almost completely removed during mineral maturation. Amelogenin interacts with the transmembrane proteins CD63 and LAMP (lysosome-associated membrane protein) 1, which are involved in endocytosis. Exogenously added amelogenin has been observed to move rapidly into CD63/LAMP1-positive vesicles in cultured cells. In the present study, we demonstrate the protein region defined by amino acid residues 103-205 for CD63 interacts not only with amelogenin, but also with other enamel matrix proteins (ameloblastin and enamelin). A detailed characterization of binding regions in amelogenin, CD63 and LAMP1 reveals that the amelogenin region defined by residues PLSPILPELPLEAW is responsible for the interaction with CD63 through residues 165-205, with LAMP1 through residues 226-251, and with the related LAMP2 protein through residues 227-259. We predict that the amelogenin binding region is: (i) hydrophobic; (ii) largely disordered; and (iii) accessible to the external environment. In contrast, the binding region of CD63 is likely to be organized in a '7' shape within the mushroom-like structure of CD63 EC2 (extracellular domain 2). In vivo, the protein interactions between the secreted enamel matrix proteins with the membrane-bound proteins are likely to occur at the specialized secretory surfaces of ameloblast cells called Tomes' processes. Such protein-protein interactions may be required to establish short-term order of the forming matrix and/or to mediate feedback signals to the transcriptional machinery of ameloblasts and/or to remove matrix protein debris during enamel biomineralization.
authors: University of Southern California School of Dentistry, Center for Craniofacial Molecular Biology, 2250 Alcazar Street, CSA Room 103, Los Angeles, CA 90033-1004, USA.
authors: YanMing
authors: Y
authors: Zou
authors: HongJun
authors: H
authors: Wang
authors: Jason L
authors: JL
authors: Shapiro
authors: Curtis T
authors: CT
authors: Okamoto
authors: Steven J
authors: SJ
authors: Brookes
authors: S Petter
authors: SP
authors: Lyngstadaas
authors: Malcolm L
authors: ML
authors: Snead
authors: Michael L
authors: ML
authors: Paine
mesh_terms: D053523:Amelogenin / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D051907:Lysosomal Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D060149:Tetraspanin 30; D020798:Two-Hybrid System Techniques; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D053523:Amelogenin; D015703:Antigens, CD; D017931:DNA Primers; D051907:Lysosomal Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; C554587:Cd63 protein, mouse; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1
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