Structural studies on extracellular adhesion GPCR signaling

粘附G蛋白偶联受体（adhesion-G-Protein-coupled Receptors，aGPCR）是一个庞大的受体家族，其生物化学、结构和功能的研究尚不全面。本项目的目的是通过X射线结构分析来研究受体的空间结构及其与结合配偶体的相互作用，为了解受体的分子功能和基于结构开发作用于受体的潜在药物奠定基础。为此，受体和单结构域在三种不同的表达系统中表达：E.大肠杆菌、HEK细胞和昆虫细胞。对于结构和生物药理学研究，需要制备毫克量的高纯蛋白质。主要研究了受体作用方式中的以下过程：配体与胞外结合结构域的结合及其引起的结合结构域与GAIN结构域相互作用中的构象变化，以及GAIN结构域与跨膜部分的相互作用，这在allaGPCR中可能是保守的。

Adhesion-G-Protein-coupled Receptors (aGPCR) are a large receptorfamily which has been only partially investigated so far concerning itsbiochemical, structural and functional properties. The aim of theproject is to characterise the spatial structures of the receptors andtheir interactions with binding partners by X-ray structure analysis.Such studies are the basis to understand the molecular function of thereceptors and for a structure-based development of potential drugsacting on these receptors. To this end, the receptors and singledomains are expressed in three different expression systems: E. coli,HEK cells and insect cells. For structural and biophysicalinvestigations milligram quantities of highly pure protein need to beprepared. The following processes in the mode of action of thereceptors will be primarily studied: The binding of ligands to theextracellular binding domains and the conformational changes in theinteraction of the binding domains and the GAIN domains inducedthereby and, furthermore, the interaction between the GAIN domainand the transmembrane part, which is probably conserved in allaGPCR.