Structure and activation of the TSH receptor transmembrane domain.

ABSTRACT:

Purpose

The thyroid-stimulating hormone receptor (TSHR) is the target autoantigen for TSHR-stimulating autoantibodies in Graves' disease. The TSHR is composed of: a leucine-rich repeat domain (LRD), a hinge region or cleavage domain (CD) and a transmembrane domain (TMD). The binding arrangements between the TSHR LRD and the thyroid-stimulating autoantibody M22 or TSH have become available from the crystal structure of the TSHR LRD-M22 complex and a comparative model of the TSHR LRD in complex with TSH, respectively. However, the mechanism by which the TMD of the TSHR and the other glycoprotein hormone receptors (GPHRs) becomes activated is unknown.

Methods

We have generated comparative models of the structures of the inactive (TMD_In) and active (TMD_Ac) conformations of the

SUBMITTER: Nunez Miguel R 

PROVIDER: S-EPMC5136658 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature