The project will leverage our understanding of a naturally occurring protein domain family to synthesise augmentable adhesive modules that target specific substrates. The candidate set of six well-studied structural homologues are members of the ‘Polymer Adhesin Domain’ family (PAD), deployed by bacteria within extracellular wall-tethered proteins that target specific sugars and glycoproteins in the Extracellular Matrix (ECM) of host tissues. The extensive structural diversity of the six PAD homologues derives from augmentation of a common core fold (the ‘scaffold’), generating distinct gated binding clefts. This leads to selective affinity for unique sugar/glycan substrates, thereby enabling specific adherence to different target tissues. This project will leverage this naturally mutable domain to create a knowledge-driven proof-of-concept study whereby the scaffold is tailored to alter the substrate specificity of a candidate domain.
