Thyroid Peroxidase as an Autoantigen in Hashimoto’s Disease: Structure, Function, and Antigenicity

Daniel E. Williams; Sarah N. Le; Marlena Godlewska; David E. Hoke; Ashley M. Buckle

doi:10.1055/a-0717-5514

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2018; 50(12): 908-921
DOI: 10.1055/a-0717-5514

Review

Thyroid Peroxidase as an Autoantigen in Hashimoto’s Disease: Structure, Function, and Antigenicity

Authors

Daniel E. Williams

¹Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Sarah N. Le

¹Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Marlena Godlewska

²Department of Biochemistry and Molecular Biology, Center of Postgraduate Medical Education, Warsaw, Poland
David E. Hoke

¹Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Ashley M. Buckle

¹Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia

Abstract

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.

Key words

thyroid peroxidise - TPO - autoantibodies - thyroid - Hashimoto’s thyroiditis

Full Text

References

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