Effect of Phosphorylation on the Interaction of Calcium with Leucine-rich Amelogenin Peptide

Overview

Journal Eur J Oral Sci

Specialty Dentistry

Date 2012 Jan 17

PMID 22243234

Citations 16

Authors

Elvire Le Norcy

Seo-Young Kwak

Marc Allaire

Peter Fratzl

Yasuo Yamakoshi

James P Simmer

Henry C Margolis

Affiliations

Soon will be listed here.

Abstract

Amelogenin undergoes self-assembly and plays an essential role in guiding enamel mineral formation. The leucine-rich amelogenin peptide (LRAP) is an alternative splice product of the amelogenin gene and is composed of the N terminus (containing the only phosphate group) and the C terminus of full-length amelogenin. This study was conducted to investigate further the role of phosphorylation in LRAP self-assembly in the presence and absence of calcium using small angle X-ray scattering (SAXS). Consistent with our previous dynamic light-scattering findings for phosphorylated (+P) and non-phosphorylated (-P) LRAP, SAXS analyses revealed radii of gyration (R(g)) for LRAP(-P) (46.3-48.0 Å) that were larger than those for LRAP(+P) (25.0-27.4 Å) at pH 7.4. However, added calcium (up to 2.5 mM) induced significant increases in the R(g) of LRAP(+P) (up to 46.4 Å), while it had relatively little effect on LRAP(-P) particle size. Furthermore, SAXS analyses suggested compact folded structures for LRAP(-P) in the presence and absence of calcium, whereas the conformation of LRAP(+P) changed from an unfolded structure to a more compact structure upon the addition of calcium. We conclude that the single phosphate group in LRAP(+P) induces functionally important conformational changes, suggesting that phosphorylation may also influence amelogenin conformation and protein-mineral interactions during the early stages of amelogenesis.

Citing Articles

Effect of phosphate group on remineralization of early enamel caries regulated by amelogenin peptide.

Zhao H, Zhang Q, Chu J PLoS One. 2024; 19(5):e0303147.

PMID: 38771806 PMC: 11108222. DOI: 10.1371/journal.pone.0303147.

Calcium interactions in amelogenin-derived peptide assembly.

Zhang J, Bai Y, Wang J, Li B, Habelitz S, Lu J Front Physiol. 2023; 13:1063970.

PMID: 36589425 PMC: 9795176. DOI: 10.3389/fphys.2022.1063970.

Loss of biological control of enamel mineralization in amelogenin-phosphorylation-deficient mice.

Stifler C, Yamazaki H, Gilbert P, Margolis H, Beniash E J Struct Biol. 2022; 214(2):107844.

PMID: 35219810 PMC: 9149128. DOI: 10.1016/j.jsb.2022.107844.

A N-Terminus Domain Determines Amelogenin's Stability to Guide the Development of Mouse Enamel Matrix.

Huang Y, Bai Y, Chang C, Bacino M, Cheng I, Li L J Bone Miner Res. 2021; 36(9):1781-1795.

PMID: 33957008 PMC: 9307086. DOI: 10.1002/jbmr.4329.

Molecular Cloning of Mouse Homologue of Enamel Protein C4orf26 and Its Phosphorylation by FAM20C.

Govitvattana N, Kaku M, Ohyama Y, Jaha H, Lin I, Mochida H Calcif Tissue Int. 2021; 109(4):445-454.

PMID: 33884476 PMC: 8429244. DOI: 10.1007/s00223-021-00847-y.

References

Doniach S . Changes in biomolecular conformation seen by small angle X-ray scattering. Chem Rev. 2001; 101(6):1763-78. DOI: 10.1021/cr990071k. View

Shaw W, Ferris K . Structure, orientation, and dynamics of the C-terminal hexapeptide of LRAP determined using solid-state NMR. J Phys Chem B. 2009; 112(51):16975-81. PMC: 2771880. DOI: 10.1021/jp808012g. View

Wang L, Guan X, Du C, Moradian-Oldak J, Nancollas G . Amelogenin Promotes the Formation of Elongated Apatite Microstructures in a Controlled Crystallization System. J Phys Chem C Nanomater Interfaces. 2010; 111(17):6398-6404. PMC: 2843430. DOI: 10.1021/jp0675429. View

He X, Wu S, Martinez-Avila O, Cheng Y, Habelitz S . Self-aligning amelogenin nanoribbons in oil-water system. J Struct Biol. 2010; 174(1):203-12. PMC: 3204882. DOI: 10.1016/j.jsb.2010.11.027. View

Aoba T, Moreno E . The enamel fluid in the early secretory stage of porcine amelogenesis: chemical composition and saturation with respect to enamel mineral. Calcif Tissue Int. 1987; 41(2):86-94. DOI: 10.1007/BF02555250. View

Paine M, Wang H, Snead M . Amelogenin self-assembly and the role of the proline located within the carboxyl-teleopeptide. Connect Tissue Res. 2003; 44 Suppl 1:52-7. View

Aichmayer B, Margolis H, Sigel R, Yamakoshi Y, Simmer J, Fratzl P . The onset of amelogenin nanosphere aggregation studied by small-angle X-ray scattering and dynamic light scattering. J Struct Biol. 2005; 151(3):239-49. DOI: 10.1016/j.jsb.2005.06.007. View

Margolis H, Beniash E, Fowler C . Role of macromolecular assembly of enamel matrix proteins in enamel formation. J Dent Res. 2006; 85(9):775-93. DOI: 10.1177/154405910608500902. View

Fincham A, Moradian-Oldak J, Sarte P . Mass-spectrographic analysis of a porcine amelogenin identifies a single phosphorylated locus. Calcif Tissue Int. 1994; 55(5):398-400. DOI: 10.1007/BF00299322. View

10.

Buchko G, Tarasevich B, Bekhazi J, Snead M, Shaw W . A solution NMR investigation into the early events of amelogenin nanosphere self-assembly initiated with sodium chloride or calcium chloride. Biochemistry. 2008; 47(50):13215-22. PMC: 2663401. DOI: 10.1021/bi8018288. View

11.

Fincham A, Moradian-Oldak J, Diekwisch T, Lyaruu D, Wright J, Bringas Jr P . Evidence for amelogenin "nanospheres" as functional components of secretory-stage enamel matrix. J Struct Biol. 1995; 115(1):50-9. DOI: 10.1006/jsbi.1995.1029. View

12.

Paine M, Snead M . Protein interactions during assembly of the enamel organic extracellular matrix. J Bone Miner Res. 1997; 12(2):221-7. DOI: 10.1359/jbmr.1997.12.2.221. View

13.

Yamakoshi Y, Tanabe T, Oida S, Hu C, Simmer J, Fukae M . Calcium binding of enamel proteins and their derivatives with emphasis on the calcium-binding domain of porcine sheathlin. Arch Oral Biol. 2001; 46(11):1005-14. DOI: 10.1016/s0003-9969(01)00070-x. View

14.

Wiedemann-Bidlack F, Beniash E, Yamakoshi Y, Simmer J, Margolis H . pH triggered self-assembly of native and recombinant amelogenins under physiological pH and temperature in vitro. J Struct Biol. 2007; 160(1):57-69. PMC: 2375294. DOI: 10.1016/j.jsb.2007.06.007. View

15.

Beniash E, Metzler R, Lam R, Gilbert P . Transient amorphous calcium phosphate in forming enamel. J Struct Biol. 2009; 166(2):133-43. PMC: 2731811. DOI: 10.1016/j.jsb.2009.02.001. View

16.

Allaire M, Yang L . Biomolecular solution X-ray scattering at the National Synchrotron Light Source. J Synchrotron Radiat. 2010; 18(1):41-4. PMC: 3004252. DOI: 10.1107/S0909049510036022. View

17.

Le Norcy E, Kwak S, Wiedemann-Bidlack F, Beniash E, Yamakoshi Y, Simmer J . Potential role of the amelogenin N-terminus in the regulation of calcium phosphate formation in vitro. Cells Tissues Organs. 2011; 194(2-4):188-93. PMC: 3178076. DOI: 10.1159/000324827. View

18.

Aichmayer B, Wiedemann-Bidlack F, Gilow C, Simmer J, Yamakoshi Y, Emmerling F . Amelogenin nanoparticles in suspension: deviations from spherical shape and pH-dependent aggregation. Biomacromolecules. 2009; 11(2):369-76. PMC: 2817559. DOI: 10.1021/bm900983b. View

19.

Nagano T, Kakegawa A, Yamakoshi Y, Tsuchiya S, Hu J, Gomi K . Mmp-20 and Klk4 cleavage site preferences for amelogenin sequences. J Dent Res. 2009; 88(9):823-8. PMC: 2751868. DOI: 10.1177/0022034509342694. View

20.

Putnam C, Hammel M, Hura G, Tainer J . X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution. Q Rev Biophys. 2007; 40(3):191-285. DOI: 10.1017/S0033583507004635. View