Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid autoimmune disease.

Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid autoimmune disease. Endocrinology. 2020 Feb 05;: Authors: Williams DE, Le SN, Hoke DE, Chandler PG, Gora M, Godlewska M, Banga JP, Buckle AM Abstract Thyroid peroxidase (TPO) is a critical membrane-bound enzyme involved in the biosynthesis of multiple thyroid hormones, and is a major autoantigen in autoimmune thyroid diseases such as destructive (Hashimoto's) thyroiditis. Here we report the biophysical and structural characterisation of two novel TPO constructs containing only the ectodomain of TPO and lacking the propeptide. Both constructs were enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultra-centrifugation data suggests that TPO can exist as both a monomer and a dimer. Combined with negative stain electron microscopy and molecular dynamics simulations, these data show that TR1.9 autoantibody preferentially binds the TPO monomer, revealing conformational changes that bring together previously disparate residues into a continuous epitope. In addition to providing plausible structural models of a TPO-autoantibody complex, this study provides validated TPO constructs that will facilitate further characterization, and advances our understanding of the structural, functional and antigenic characteristics of TPO, an autoantigen behind some of the most common autoimmune diseases. PMID: ...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research