Endocrine Abstracts

The sequence–structure–function-analysis of glycoprotein hormone receptors (SSFA-GPHR) database provides a comprehensive set of mutation data for the glycoprotein hormone receptors (covering the lutropin – (LHCGR), the follitropin (FSHR) and the thyrotropin receptor (TSHR)). Numerous databases present functional information along with pooled data from various public resources, but tools to analyse the molecular effects of genetic variations are as yet poorly provided. Besides extending the dataset (>1100 mutations), the database has been completely redesigned and several novel features and analysis tools have been added. These tools allow the focused extraction of semi-quantitative mutant data from the GPHR subtypes and different experimental approaches. Functional data of the GPHRs are now linked interactively at the web interface with protein structure data and novel tools for data search and visualization are provided. A user defined 2D-search option via snake plots highlights the requested mutated residue(s) in a two dimensional representation of the sequence of interest and hyperlinks them to the mutation information. A 3D-search serves as interactive picking option of any residue position of interest on a 3D structure and provides information about functional effects of available genetic variations that can be mapped onto the structure. The new receptor morphing simulation tool permits tracing of potential structural changes from the basal to an activated receptor conformation for any individual wild type residue and provides clues to the local structural environment, including potentially relocated spatial counterpart residues. Furthermore, double and triple mutations are newly included to allow the analysis of their functional effects related to their spatial interrelationship in structures or homology models. These new tools can be used to identify interacting residues as counterparts and to evaluate potential mechanisms of molecular malfunction caused by specific mutations and give thereby deeper insights in the mechanisms of hormone binding, signal transduction and signaling regulation of GPHRs.