Structural characterisation of phosphopeptide recognition by FHA domains

细胞需要许多信号通路来协调和控制各种细胞过程。信号传导最重要的方面之一是涉及两种或多种不同蛋白质的复合物的形成。最近确定的这些信号复合物形成中的参与者之一是所谓的叉头相关（FHA）模块，FHA模块是约130个氨基酸的蛋白质序列，其作为信号蛋白的一部分出现并结合到信号蛋白伴侣上的特定序列。许多含有FHA模块的蛋白质对于受损DNA的修复和染色体的稳定性是重要的。我们研究的目的是了解FHA模块如何结合其伴侣的分子和原子细节。这是设计针对DNA受损的各种癌症的治疗剂的第一步。

Cells require numerous signalling pathways to keep various cellular processes coordinated and under control. One of the most important aspects of signalling is formation of complexes involving two or more different proteins. One of the recently identified players in the formation of these signalling complexes is the so-called forkhead-associated (FHA) module, FHA modules are protein sequences of ~130 amino acids that appear as a part of signalling proteins and bind to specific sequences on signalling protein partners. Many proteins containing FHA modules are important for the repair of damaged DNA and the stability of chromosomes. The aim of our studies is to understand the molecular and atomic details of how FHA modules bind their partners. This is the first step towards designing therapeutic agents against various forms of cancer where DNA is damaged.