STATISTICAL-ANALYSIS OF FUNCTIONAL REGION(S) OF THE TSH RECEPTOR

in this study, we apply recently developed methods to evaluate the thy rotropin receptor (TSH-R). These methods are called deviation (DEV) mo del, deviation decrease (DD) and DEV/DD analyses, and are based on dev iation of amino acid sequences. A 3-dimensional structure model of TSH -R was graphically constructed, and found to possess a large central c avity (donut-like structure), The N-terminus was found to be in the ce nter of the whole extracellular structure and to form a part of the bo ttom of the cavity. High DEV values indicate deviated amino acid compo sitions in the protein and were seen in 7 regions, 6 of which were fou nd to be in regions with hydrophilic and acrophilic character, On the basis of the analysis of intra-molecular cis-acting relationships, 7 p airs of regions were presumed to be closely related, Further, when 3 e xoplasmic loop lesions were analyzed similarly, 3 other regions were s hown to have a close relationship with the cell surface, DEV/DD values were applied to predict the interface of TSH-R with trans-acting mole cules such as TSH-R antibody or TSH, The regions in association with t rans-acting molecules were seen in 14 regions, 11 of which included th e high DEV regions. Both of the TSH-R specific regions in the N- and C -terminal side, especially the latter, were found to be the major comp onents.