Complement system

The interactions that occur at the interface between the human host and the myriad bacterial microorganisms with which we come into daily contact constitute a topic of profound significance, both at a fundamental biological level and as an area of expanding medical interest. On the one hand, the bacterial communities that inhabit us (the microbiome) establish interactions that are mostly neutral, beneficial, and even protective for us in the face of invading pathogens. On the other hand, pathogens must interact with our cells and those of the microbiome as a prerequisite for a successful infection. The nature of those interactions vary from physical interactions mediated by protein complexes (e.g., receptor-ligand complexes) to functional interactions (e.g., metabolic coupling, prodrug conversion).

The complement system of the innate immunity stands as one of the first defence barriers against pathogens. The human complement system is a collection of soluble and membrane-associated proteins that monitor the blood and tissue interstitial fluids for pathogens, apoptotic cells and immune complexes. In addition to its prominent role in innate immunity, complement also modulates the adaptive immune system. Pathogens have evolved sophisticated molecular weaponry that allows them to escape surveillance from the complement system, a strategy designated immunoevasion. In this context, we are focused in elucidating the structures and mechanistic details of the complement system components and their protein complexes with virulence factors with immunoevasive properties.

In all those different scenarios, structural biology plays a central role in advancing our understanding of the atomic-level communication between host and bacteria. This greater knowledge will afford deeper insights into the manifold biological, immunological, and metabolic processes involved in the complex interplay between hosts and pathogens. Furthermore, increasing our understanding of these processes at the atomic level is crucial to develop potential treatments against many diseases.