Archived Issues

We congratulate you on acceptance of your manuscript.

Browse by Year

Advancements in the Structural Resolution of Bovine Thyroglobulin

August 30, 2019

Abstract – Thyroglobulin is a protein located in the thyroid and controls hormone production. These hormones work to modulate behavior, central nervous system function, and energy metabolism in vertebrates (Holzer et al., 2016). In addition, it is a dimeric glycoprotein with a molecular mass of 660 kDa. Specifically, bovine thyroglobulin is heavily decorated with alpha-gal and can be used to diagnose the red meat allergy (Apostolovic et al., 2017). For these reasons, the structure of bovine thyroglobulin is crucial to find and can lead to new information about the relationship between alpha-gal and the IgE antibodies.
 Keywords – bovine thyroglobulin, alpha-gal, IgE antibodies


Introduction: Alpha-gal, an oligosaccharide, is a major blood group substance in mammals such as cattle and pigs. Studies strongly suggest that bites from the Lone Star Tick Amblyomma americanum infect the human host with the carbohydrate alpha-gal (Commins & Platts-Mills, 2013). After some time, when beef or another red meat is consumed, an immune response is initiated by the IgE antibodies, that results in an immediate allergic reaction characterized by symptoms of anaphylaxis (Sim et al., 2017). Currently, the structure of bovine thyroglobulin is unresolved. The aim of this research was to determine the molecular structure of bovine thyroglobulin using Macromolecular crystallography (MX) and Small Angle X-ray Scattering (SAXS). With MX, the aim was to test whether lysozyme is a nucleation inducing reagent of thyroglobulin, and with SAXS, the aims were to obtain a low-resolution image of the structure of bovine thyroglobulin and discover the bead model of bovine thyroglobulin. It was hypothesized that lysozyme will aid in the crystallization in thyroglobulin and that the bead model will be a complex globular structure containing alpha and beta helices, factoring inflexibility. 


References

  1. Apostolovic, D., Krstic, M., Mihailovic, J., Starkhammar, M., Velickovic, T. C., Hamsten, C., & van Hage, M. (2017). Peptidomics of an in vitro digested α-Gal carrying protein revealed IgE-reactive peptides. Scientific reports, 7(1), 5201. 

  2. Benkert, P., Biasini, M., Schwede, T. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27, 343-350 (2011). 


  3. Bertoni, M., Kiefer, F., Biasini, M., Bordoli, L., Schwede, T. Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Scientific Reports 7 (2017). 


  4. Biosis. (2013). PRIMUS (WINDOWS ONLY). Retrieved from 
http://www.bioisis.net/tutorial/4 
http://iramis.cea.fr/Phocea/Vie_des_labos/Ast/ast_sstechnique.php?id_ast=1065 


  5. Bruno Di Jeso, Peter Arvan; Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology, Endocrine Reviews, Volume 37, Issue 1, 1 February 2016, Pages 2–36, https://doi.org/10.1210/er.2015-1090 


  6. Commins, S. P., & Platts-Mills, T. E. (2013). Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (alpha-gal). Current Allergy And Asthma Reports, 13(1), 72-77. doi:10.1007/s11882-012-0315-y 


  7. Edelhoch, H., J. Biol. Chem., 235, 1326 (1960). 


  8. Franke, D., Petoukhov, M.V., Konarev, P.V., Panjkovich, A., Tuukkanen, A., Mertens, 
H.D.T., Kikhney, A.G., Hajizadeh, N.R., Franklin, J.M., Jeffries, C.M. and Svergun, D.I. (2017) ATSAS 2.8: a comprehensive data analysis suite for small-angle scattering from macromolecular solutions J. Appl. Cryst. 50, 1212-1225 


  9. Gentile, F., Salvatore, G., & Salvatore, G. (1995). Molecular heterogeneity of covalently-linked bovine thyroglobulin dimers. Rendiconti Lincei, 6(2), 165.
Holzer, G., Lorin, T., Gillet, B., Hughes, S., Tohme, M., Laudet, V., & ... Deleage, G. (n.d). Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates. Journal Of Biological Chemistry, 291(32), 16553-+. 


  10. Jakoby, W. B., Labaw, L., Edelhoch, H., Pastan, I., & Rall, J. E. (1966). Thyroglobulin: Evidence for Crystallization and Association. Science, 153(3744), 1671-1672. doi:10.1126/science.153.3744.1671 


  11. Leszczyszyn, O., Hydrodynamic Radius. (2018, December 11). Retrieved from
https://www.materials-talks.com/blog/2012/11/15/size-matters-rh-versus-rg/