Plug-and-Play Streptavidin Hubs for Megaprotein Assembly and Nanoscale Control of Cell-Surface Triggering

数量上有力量，甚至在分子水平上也是如此。团簇中的生物分子通常具有孤立的这些分子无法实现的效果。众所周知，如何使用一种名为链霉亲和素的蛋白质，将一个生物分子聚集成四人一组。链霉亲和素是生物学研究和生物技术中使用最广泛的工具之一，因为它具有高效和稳定的聚集性。在这项提案中，我们将确定如何设计链霉亲和素，以建立一系列包含精确分子数量的更大簇，最高可达33个。除了确定如何建立不同大小和方向的牢不可破的星系团的规则外，我们的新星系团将成为研究和控制许多生物事件的强大工具。信号通常通过细胞表面的蛋白质簇传递给细胞。杀手T细胞在体内巡逻，仔细观察它们传递的细胞，以确定该细胞是否感染或健康。根据T细胞上受体聚集的组织，T细胞可能会杀死目标细胞，也可能不会对其造成伤害。我们将应用我们的不同簇来理解T细胞如何做出这一关键决定。

There is strength in numbers, even at the molecular level. Biological molecules in clusters often have effects that cannot be achieved by those molecules in isolation. It is well known how to cluster one biological molecule into teams of 4, using a protein called streptavidin. Streptavidin is one of the most widely used tools in biological research and biotechnology because of this efficient and stable clustering. In this proposal we will establish how to engineer streptavidin to build a range of larger clusters containing precise numbers of molecules, up to 33. As well as determining the rules for how to build unbreakable clusters of different size and orientation, our new clusters will be powerful tools for studying and controlling many biological events. Signals are often communicated to cells through clustering of proteins at their surface. Killer T cells patrol the body, scrutinising the cells they pass to determine whether that cell is infected or healthy. According to the organisation of the clustering of receptors on the T cell, the T cell may kill the target cell or leave it unharmed. We will apply our different clusters to understand how the T cell makes this crucial decision.