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Structural Studies of Thyroid Peroxidase Show the Monomer Interacting With Autoantibodies in Thyroid Autoimmune Disease

Endocrinology. 2020; 
Williams DE, Le SN, Hoke DE, Chandler PG, Gora M, Godlewska M, Banga JP, Buckle AM.
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Gene Synthesis Both plasmid products were digested with BamHI, ligated and then transformed into chemically competent DH5α The gene for the yeast GCN4 dimerisation motif was chemically synthesised (GenScript) and subcloned with NotI and BamHI into the pUC57 ampicillin resistant vector containing the C- terminal ΔproTPOe sequence. Get A Quote

摘要

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) thyroiditis. Here we report the biophysical and structural characterization of a novel TPO construct containing only the ectodomain of TPO and lacking the propeptide. The construct was enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultracentrifugation data suggest 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 the TR1.9 autoantibody preferentially binds the... More

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