ERA NANOSCI: Observation and manipulation of individual type I interferon signalling complexes

跨膜多蛋白复合物的配体识别是通过蛋白质相互作用和构象变化的复杂相互作用来传播的。这些复合物的动态性质和跨膜结构迄今为止阻碍了对分子水平上信号转导机制的理解。此外，局部微结构在质膜中的重要作用已经变得明显。我们的目的是研究个体I型干扰素信号复合体重组成结构模型膜。配体相互作用动力学，构象变化及其通过膜的传播将使用单对荧光共振能量转移来确定。相互作用的能量格局将通过单分子力谱来探测。结合生化方法，微加工技术和单分子检测将提供一个独特的机会来全面探索最重要的生物过程之一。

Ligand recognition by transmembrane multi-protein complexes is propagated by y complex interplay of protein interactions and conformational changes. The dynamic nature of these complexes and the transmembrane architecture ha so far impeded unerstanding of signal transduction mechanism on the molecular level. Furthermore, an important role of local microstructures in the plasma membrane has become evifent. We aim to investigate individual type I interferon signalling complexes reconsti-tuted into structured model membranes. Ligand interaction dynamics, conformational changes and their propagation through the membrane will be determided using single-pair fluorescene resonance energy transfer. The energy landscape of the interactions will be probed by single molecule force spectroscopy. Combining biochemical methods, micro-fabrication techniques and single-molecule detection will provide a unique opportunity to comprehensively explore one of the most important biological processes.