TSH receptor–autoantibodies interactions

Núñez Miguel et al. describe the crystal structure of a new human thyroid-stimulating MAb K1–18 and a predicted model of K1–18 binding to the TSHR LRD (TSH receptor – Leucine-rich domain). Furthermore, they also describe the predicted model of TSHR LRD bound to a thyroid-blocking mouse MAb RSR-B2, for which a high-resolution crystal structure was available.

The available crystal structures of the TSHR in complex with M22 and K–70 provide valuable insight into how a stimulating and a blocking antibody bind to the TSHR and, together with extensive experimental studies, suggest that these arrangements reflect binding of TSHR antibodies in general. In the absence of further crystal structures of the TSHR in complex with other antibodies, they used charge–charge interaction mapping methodology to predict binding of a new thyroid-stimulating human MAb K1–18 and a thyroid-blocking mouse MAb RSR-B2 with the TSHR. The predicted binding arrangements were validated by the effects of the TSHR amino acid mutations on the biological activity of the MAbs, and the binding arrangements of the TSHR LRD with two stimulating (M22 and K1–18) and two blocking MAbs (K1–70 and RSR-B2) were compared. Núñez Miguel et al. (2012) Journal of Molecular Endocrinology 49 137-151.

Read the full article at: DOI: 10.1530/JME-12-0040