Thyroid Peroxidase as an Autoantigen in Hashimoto's Disease: Structure, Function, and Antigenicity. 2018

Daniel E Williams, and Sarah N Le, and Marlena Godlewska, and David E Hoke, and Ashley M Buckle
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

Human thyroid peroxidase (TPO), is an important enzyme responsible for the biosynthesis of thyroid hormones and is a major autoantigen in autoimmune thyroid diseases (AITDs) such as the destructive Hashimoto's thyroiditis. Although the structure of TPO has yet to be determined, its extracellular domain consists of three regions that exhibit a high degree of sequence similarity to domains of known three-dimensional structure: the myeloperoxidase (MPO)-like domain, complement control protein (CCP)-like domain, and epidermal growth factor (EGF)-like domain. Homology models of TPO can therefore be constructed, providing some structural context to its known function, as well as facilitating the mapping of regions that are responsible for its autoantigenicity. In this review, we highlight recent progress in this area, in particular how a molecular modelling approach has advanced the visualisation and interpretation of epitope mapping studies for TPO, facilitating the dissection of the interplay between TPO protein structure, function, and autoantigenticity.

UI MeSH Term Description Entries
D007453 Iodide Peroxidase A hemeprotein that catalyzes the oxidation of the iodide radical to iodine with the subsequent iodination of many organic compounds, particularly proteins. EC 1.11.1.8. Iodinase,Iodothyronine 5'-Deiodinase,Iodothyronine Deiodinase,Iodotyrosine Deiodase,Thyroid Peroxidase,Thyroxine 5'-Deiodinase,Thyroxine 5'-Monodeiodinase,5'-Deiodinase,Deiodinase,Iodotyrosine Deiodinase,Monodeiodinase,Reverse Triiodothyronine 5'-Deiodinase,T4-5'-Deiodinase,T4-Monodeiodinase,Tetraiodothyronine 5'-Deiodinase,Thyroxine Converting Enzyme,Triiodothyronine Deiodinase,5' Deiodinase,5'-Deiodinase, Iodothyronine,5'-Deiodinase, Reverse Triiodothyronine,5'-Deiodinase, Tetraiodothyronine,5'-Deiodinase, Thyroxine,5'-Monodeiodinase, Thyroxine,Deiodase, Iodotyrosine,Deiodinase, Iodothyronine,Deiodinase, Iodotyrosine,Deiodinase, Triiodothyronine,Enzyme, Thyroxine Converting,Iodothyronine 5' Deiodinase,Peroxidase, Iodide,Peroxidase, Thyroid,Reverse Triiodothyronine 5' Deiodinase,T4 5' Deiodinase,T4 Monodeiodinase,Tetraiodothyronine 5' Deiodinase,Thyroxine 5' Deiodinase,Thyroxine 5' Monodeiodinase,Triiodothyronine 5'-Deiodinase, Reverse
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000939 Epitopes Sites on an antigen that interact with specific antibodies. Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D001324 Autoantigens Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response. Autoantigen,Autologous Antigen,Autologous Antigens,Self-Antigen,Self-Antigens,Antigen, Autologous,Antigens, Autologous,Self Antigen,Self Antigens
D015202 Protein Engineering Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes. Genetic Engineering of Proteins,Genetic Engineering, Protein,Proteins, Genetic Engineering,Engineering, Protein,Engineering, Protein Genetic,Protein Genetic Engineering
D050031 Hashimoto Disease Chronic autoimmune thyroiditis, characterized by the presence of high serum thyroid AUTOANTIBODIES; GOITER; and HYPOTHYROIDISM. Hashimoto's Disease,Chronic Lymphocytic Thyroiditis,Hashimoto Struma,Hashimoto Thyroiditis,Hashimoto's Struma,Hashimoto's Syndrome,Chronic Lymphocytic Thyroiditides,Disease, Hashimoto,Disease, Hashimoto's,Hashimoto Syndrome,Hashimoto Thyroiditides,Hashimoto's Syndromes,Hashimotos Disease,Hashimotos Syndrome,Lymphocytic Thyroiditides, Chronic,Lymphocytic Thyroiditis, Chronic,Syndrome, Hashimoto's,Syndromes, Hashimoto's,Thyroiditides, Chronic Lymphocytic,Thyroiditides, Hashimoto,Thyroiditis, Chronic Lymphocytic,Thyroiditis, Hashimoto
D040681 Structural Homology, Protein The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN. Protein Structural Homology,3-D Homologs, Protein,3-D Homology, Protein,3-Dimensional Homologs, Protein,3-Dimensional Homology, Protein,Homologs, 3-D, Protein,Homologs, 3-Dimensional, Protein,Homologs, Sturctural, Protein,Protein Structural Homologs,Structural Homologs, Protein,3 D Homologs, Protein,3 D Homology, Protein,3 Dimensional Homologs, Protein,3 Dimensional Homology, Protein,3-D Homolog, Protein,3-D Homologies, Protein,3-Dimensional Homolog, Protein,3-Dimensional Homologies, Protein,Homolog, Protein 3-D,Homolog, Protein 3-Dimensional,Homolog, Protein Structural,Homologies, Protein 3-D,Homologies, Protein 3-Dimensional,Homologies, Protein Structural,Homologs, Protein 3-D,Homologs, Protein 3-Dimensional,Homologs, Protein Structural,Homology, Protein 3-D,Homology, Protein 3-Dimensional,Homology, Protein Structural,Protein 3-D Homolog,Protein 3-D Homologies,Protein 3-D Homologs,Protein 3-D Homology,Protein 3-Dimensional Homolog,Protein 3-Dimensional Homologies,Protein 3-Dimensional Homologs,Protein 3-Dimensional Homology,Protein Structural Homolog,Protein Structural Homologies,Structural Homolog, Protein,Structural Homologies, Protein

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