Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif

0474116 - MBÚ 2018 RIV US eng J - Článek v odborném periodiku
Wald, Tomáš - Špoutil, František - Osičková, Adriana - Procházková, Michaela - Benada, Oldřich - Kašpárek, Petr - Bumba, Ladislav - Klein, O. D. - Sedláček, Radislav - Šebo, Peter - Procházka, Jan - Osička, Radim
Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 114, č. 9 (2017), s. 1641-1650. ISSN 0027-8424. E-ISSN 1091-6490
Grant CEP: GA MŠMT(CZ) LM2015064; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) LM2011032; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LO1509; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT ED2.1.00/19.0395
Grant ostatní: Ministerstvo pro místní rozvoj(CZ) CZ2.16/3.1.00/24023
Institucionální podpora: RVO:61388971 ; RVO:68378050
Klíčová slova: ameloblastin * amelogenin * biomineralization
Obor OECD: Microbiology; Microbiology (UMG-J)
Impakt faktor: 9.504, rok: 2017

The formation of mineralized tissues is governed by extracellular matrix proteins that assemble into a 3D organic matrix directing the deposition of hydroxyapatite. Although the formation of bones and dentin depends on the self-assembly of type I collagen via the Gly-X-Y motif, the molecular mechanism by which enamel matrix proteins (EMPs) assemble into the organic matrix remains poorly understood. Here we identified a Y/F-x-x-Y/L/F-x-Y/F motif, evolutionarily conserved from the first tetrapods to man, that is crucial for higher order structure self-assembly of the key intrinsically disordered EMPs, ameloblastin and amelogenin. Using targeted mutations in mice and high-resolution imaging, we show that impairment of ameloblastin self-assembly causes disorganization of the enamel organic matrix and yields enamel with disordered hydroxyapatite crystallites. These findings define a paradigm for the molecular mechanism by which the EMPs self-assemble into supramolecular structures and demonstrate that this process is crucial for organization of the organic matrix and formation of properly structured enamel.
Trvalý link: http://hdl.handle.net/11104/0271237