Structural studies on extracellular adhesion GPCR signaling

黏附- g蛋白偶联受体（aGPCR）是一个庞大的受体家族，迄今为止仅对其生化、结构和功能特性进行了部分研究。该项目的目的是通过x射线结构分析来表征受体的空间结构及其与结合伙伴的相互作用。这些研究是了解受体分子功能的基础，也是基于结构开发作用于这些受体的潜在药物的基础。为此，受体和单结构域在三种不同的表达系统中表达：大肠杆菌、HEK细胞和昆虫细胞。对于结构和生物物理研究，需要准备毫克量的高纯度蛋白质。这些受体的作用模式将主要研究以下过程：配体与细胞外结合域的结合以及由此诱导的结合域与GAIN域相互作用的构象变化，以及GAIN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.