A comparative analysis of key tooth proteins: exploring similarities and differences for dental research

Güler Burcu Senirkentli; Gazi Erkan Bostancı; Engin Koçak

doi:10.33769/aupse.1687361

A comparative analysis of key tooth proteins: exploring similarities and differences for dental research

Abstract

Tooth development is orchestrated by a set of specialized proteins integral to enamel formation. In this study, we investigate the structural and functional similarities and divergences of four pivotal enamel matrix proteins—ameloblastin, amelogenin, tuftelin, and enamelin—across Homo sapiens, Mus musculus, and Rattus norvegicus, with the central aim of elucidating conserved elements and species-specific adaptations that reflect evolutionary shaping of enamel protein function. Through computational strategies, we characterize global structural convergence by Principal Component Analysis (PCA), assess flexibility via Secondary Structure Element (SSE) analysis and B-factor profiling, probe intrinsic motion patterns using Normal Mode Analysis (NMA), quantify interspecies structural deviation by Root Mean Square Deviation (RMSD), and estimate relative stability by FoldX energy minimization. Our findings reveal a pronounced structural conservation among all four proteins, particularly within core functional domains, indicative of a shared evolutionary origin, as corroborated by PCA clustering. Nonetheless, we observe clear differences in flexibility, dynamic behavior, and stability: SSE and B-factor analyses underscore species-dependent variation in plasticity, NMA demonstrates divergence in intrinsic motions, and RMSD plus FoldX data uncover subtle but meaningful stability shifts. These structural nuances likely correspond to species-specific adaptations, perhaps linked to variations in enamel thickness, tooth morphology, or timing of development. Altogether, this comparative analysis deepens our understanding of both evolutionary conservation and functional divergence among enamel matrix proteins, offering insights with potential relevance for evolutionary biology, dental tissue engineering, and regenerative medicine, as well as a conceptual foundation for the rational design of biomimetic materials that replicate the inherent properties of dental enamel.

Keywords

References

Gil-Bona, A., & Bidlack, F. B., Tooth Enamel and Its Dynamic Protein Matrix, Int. J. Mol. Sci., 21 (12) (2020), 4458. https://doi.org/10.3390/ijms21124458
Bartlett, J. D., Dental enamel development: Proteinases and their enamel matrix substrates, ISRN Dent., (2013), 684607. https://doi.org/10.1155/2013/684607
Davis, K. A., Mountain, R. V., Pickett, O. R., Den Besten, P. K., Bidlack, F. B., & Dunn, E. C., Teeth as Potential New Tools to Measure Early-Life Adversity and Subsequent Mental Health Risk: An Interdisciplinary Review and Conceptual Model, Biol. Psychiatry, 87 (2020), 502–513. https://doi.org/10.1016/j.biopsych.2019.09.030
Queen Mary University of London-Institute of Dentistry-Barts and The London Atlas of Tooth Development and Eruption. Available online:https://www.qmul.ac.uk/dentistry/atlas/
Barre-Sinoussi, F., & Montagutelli, X., Animal models are essential to biological research: Issues and perspectives, Future Sci. OA, 1 (2015), FSO63.
Coxon, T. L., Brook, A. H., Barron, M. J., & Smith, R. N., Phenotype-genotype correlations in mouse models of amelogenesis imperfecta caused by Amelx and Enam mutations, Cells Tissues Organs, 196 (5) (2012), 420-430. https://doi.org/10.1159/000336440
DeTeruel, J. D., Alcolea, A., Hernandez, A., & Ruiz, A. J., Comparison of chemical composition of enamel and dentine in human, bovine, porcine, and ovine teeth, Arch. Oral Biol., 60 (2015), 768–775.
Karn, R. C., Chung, A. G., & Laukaitis, C. M., Shared and unique proteins in human, mouse, and rat saliva proteomes: Footprints of functional adaptation, Proteomes, 1 (3) (2013), 275-289. https://doi.org/10.3390/proteomes1030275

Species-specific protein sequence and fold optimizations, BMC Bioinform., 3 (2002), 39. https://doi.org/10.1186/1471-2105-3-39
Gollery, M., Harper, J., Cushman, J., Mittler, T., Girke, T., Zhu, J. K., Bailey-Serres, J., & Mittler, R., What makes species unique? The contribution of proteins with obscure features, Genome Biol., 7 (7) (2006), R57. https://doi.org/10.1186/gb-2006-7-7-r57
Protein Analysis Techniques Explained, ATA Scientific. Available online: https://www.atascientific.com.au/3-protein-analysis-techniques/ (Accessed: 17.05.2024)
Chitipothu, M. D., Chowdary, D., Chandrashekar, P., & Nartey, N. O., Animal Models of Relevance to Dentistry, Open Access Lib. J., 9 (5) (2022), 1-13.
Kushali, R., Maiti, S., & Geetha, R. V., Animal Model Used in Dentistry-A Review, Indian J. Forensic Med. Toxicol., 14 (4) (2020), 4534-4543.
The UniProt Consortium, UniProt: the Universal Protein Knowledgebase in 2023, Nucleic Acids Res., 51 (D1) (2023), D523–D531.
Chitipothu, M. D., Chowdary, D., Chandrashekar, P., & Nartey, N. O., Animal Models of Relevance to Dentistry, Open Access Lib. J., 9 (5) (2022), 1-13.
Muthanandam, S., Muthu, J., Mony, V., Parvathy, R. L., Prem Lal, K., Animal models in dental research – A review, Int. Dent. J. Stud. Res., 8 (2) (2020), 44-47.
Yang, S., Li, M., Yang, J., & Zhang, Y., Folding free energy landscapes reveal distinct classes of stable proteins, Cell Res., 25 (1) (2015), 89-102.
Bachmanov, A. A., Reed, D. R., Ninomiya, Y., Inoue, M., Tordoff, M. G., Price, R. A., & Beauchamp, G. K., Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses, Mamm. Genome, 8 (8) (1997), 545-548. https://doi.org/10.1007/s003359900500
Theobald, D. L., Determination of the effective protein folding landscape: Tertiary structures and packing density, Biopolymers, 55 (3) (2000), 135-148.
Krivov, S. V., The Free Energy Landscape Analysis of Protein (FIP35) Folding Dynamics, J. Phys. Chem. B, 115 (42) (2011), 12315-12324.
Li, M., Shang, Y., & Brüger, A., Normal mode analysis in studying protein dynamics, Biochim. Biophys. Acta Proteins Mol. Biol., 1854 (12) (2015), 1768-1779.
Edgar, R. C., MUSCLE: multiple sequence alignment with high accuracy and high throughput, Nucleic Acids Res., 32 (5) (2004), 1792-1797.
Wells, M., B-factor analysis in protein crystallography, Acta Crystallogr. D Struct. Biol., 72 (1) (2016), 8-20.
Grant, B. J., Skjaerven, L., & Yao, X. Q., The Bio3D packages for structural bioinformatics, Protein Sci., 30 (1) (2021), 20-30. https://doi.org/10.1002/pro.3923
Schymkowitz, J., Borg, J., Stricher, F., Nys, R., Rousseau, F., & Serrano, L., The FoldX web server: an online force field, Nucleic Acids Res., 33 (2005), W382-W388. https://doi.org/10.1093/nar/gki387
Moradian-Oldak, J., Protein-mediated enamel mineralization, Front. Biosci. Landmark Ed., 17 (6) (2012), 1996-2023. https://doi.org/10.2741/4034
Bronckers, J. J., D’Souza, R. N., & Bartlett, J. D., Enamel development: molecular and cellular events during amelogenesis, Connect. Tissue Res., 54 (2) (2013), 169-198.
Wise, L. D., & Jr, H. G., The ethics of using animals in dental research, J. Dent. Res., 81 (1) (2002), 6-10.
Loo, J. A., Yan, W., Ramachandran, P., & Wong, D. T., Comparative human salivary and plasma proteomes, J. Dent. Res., 89 (10) (2010), 1016-1023. https://doi.org/10.1177/0022034510380414
Karn, R. C., Chung, A. G., & Laukaitis, C. M., Shared and unique proteins in human, mouse, and rat saliva proteomes: Footprints of functional adaptation, Proteomes, 1 (3) (2013), 275-289.
Cruvinel, V. R., Gravina, D. B., Azevedo, T. D. P. L., Rezende, C. S., Bezerra, A. C., & Toledo, O. A., Prevalence of enamel defects and associated risk factors in both dentitions in preterm and full-term born children, J. Appl. Oral Sci., 20 (3) (2012), 310–317. https://doi.org/10.1590/s1678-77572012000300003
Pugach, M. K., & Gibson, C. W., Analysis of enamel development using murine model systems: approaches and limitations, Front. Physiol., 17 (5) (2014), 313. https://doi.org/10.3389/fphys.2014.00313

Details

Primary Language

English

Subjects

Modelling and Simulation

Journal Section

Research Article

Authors

Güler Burcu Senirkentli
0000-0003-4918-5504
Türkiye

Gazi Erkan Bostancı ^*
0000-0001-8547-7569
Türkiye

Engin Koçak
0000-0002-1076-1300
Türkiye

Publication Date

December 24, 2025

Submission Date

April 30, 2025

Acceptance Date

May 13, 2025

Published in Issue

Year 2025 Volume: 67 Number: 2

DOI

https://doi.org/10.33769/aupse.1687361

IZ

https://izlik.org/JA59SB68FC

Cite

RIS / Bibtex

APA

Senirkentli, G. B., Bostancı, G. E., & Koçak, E. (2025). A comparative analysis of key tooth proteins: exploring similarities and differences for dental research. Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering, 67(2), 153-173. https://doi.org/10.33769/aupse.1687361

AMA

1.Senirkentli GB, Bostancı GE, Koçak E. A comparative analysis of key tooth proteins: exploring similarities and differences for dental research. Commun.Fac.Sci.Univ.Ank.Series A2-A3: Phys.Sci. and Eng. 2025;67(2):153-173. doi:10.33769/aupse.1687361

Chicago

Senirkentli, Güler Burcu, Gazi Erkan Bostancı, and Engin Koçak. 2025. “A Comparative Analysis of Key Tooth Proteins: Exploring Similarities and Differences for Dental Research”. Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering 67 (2): 153-73. https://doi.org/10.33769/aupse.1687361.

EndNote

Senirkentli GB, Bostancı GE, Koçak E (December 1, 2025) A comparative analysis of key tooth proteins: exploring similarities and differences for dental research. Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering 67 2 153–173.

IEEE

[1]G. B. Senirkentli, G. E. Bostancı, and E. Koçak, “A comparative analysis of key tooth proteins: exploring similarities and differences for dental research”, Commun.Fac.Sci.Univ.Ank.Series A2-A3: Phys.Sci. and Eng., vol. 67, no. 2, pp. 153–173, Dec. 2025, doi: 10.33769/aupse.1687361.

ISNAD

Senirkentli, Güler Burcu - Bostancı, Gazi Erkan - Koçak, Engin. “A Comparative Analysis of Key Tooth Proteins: Exploring Similarities and Differences for Dental Research”. Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering 67/2 (December 1, 2025): 153-173. https://doi.org/10.33769/aupse.1687361.

JAMA

1.Senirkentli GB, Bostancı GE, Koçak E. A comparative analysis of key tooth proteins: exploring similarities and differences for dental research. Commun.Fac.Sci.Univ.Ank.Series A2-A3: Phys.Sci. and Eng. 2025;67:153–173.

MLA

Senirkentli, Güler Burcu, et al. “A Comparative Analysis of Key Tooth Proteins: Exploring Similarities and Differences for Dental Research”. Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering, vol. 67, no. 2, Dec. 2025, pp. 153-7, doi:10.33769/aupse.1687361.

Vancouver

1.Güler Burcu Senirkentli, Gazi Erkan Bostancı, Engin Koçak. A comparative analysis of key tooth proteins: exploring similarities and differences for dental research. Commun.Fac.Sci.Univ.Ank.Series A2-A3: Phys.Sci. and Eng. 2025 Dec. 1;67(2):153-7. doi:10.33769/aupse.1687361