Comparative analysis of human and bovine thyroglobulin structures

Abstract

Abstract In biology, evolutionary conserved protein sequences show homologous physiological phenotypes in their structures and functions. If the protein has a vital function, its sequence is usually conserved across the species. However, in highly conserved protein there still remains small differences across the species. Upon protein–protein interaction (PPI), it is observed that the conserved proteins can have different binding partners that are considered to be caused by the small sequence variations in a specific domain. Thyroglobulin (TG) is the most commonly found protein in the thyroid gland of vertebrates and serves as the precursor of the thyroid hormones, tetraiodothyronine and triiodothyronine that are critical for growth, development and metabolism in vertebrates. In this study, we comparatively analyzed the sequences and structures of the highly conserved regions of TG from two different species in relation to their PPIs. In order to do so, we employed SIM for sequence alignment, STRING for PPI analysis and cryo-electron microscopy for 3D structural analysis. Our Cryo-EM model for TG of Bos taurus determined at 7.1 Å resolution fitted well with the previously published Cryo-EM model for Homo sapiens TG. By demonstrating overall structural homology between TGs from different species, we address that local amino acid sequence variation is sufficient to alter PPIs specific for the organism. We predict that our result will contribute to a deeper understanding in the evolutionary pattern applicable to many other proteins.

Keywords

• Protein–protein interaction
• Conserved protein
• Transmission electron microscopy
• Cryo-electron microscopy
• Thyroglobulin