X-ray Crystallographic Studies of Human Complement Factor I

Structural biology is naturally attractive and lends itself to drawing the general public into consideration of science. SML has previously talked to school children (ranging in age from 5-18 years) about how structures can help us learn about the viruses and bacteria that make us ill. This work would be likely to generate results that would be accessible for the general public and we would therefore seek to take up all possible opportunities to interact with and inform the general public. We have recent experience in preparing exhibits for an ?Art of Science? exhibition held in Oxford and found that illustrations based on atomic coordinates derived from pathogens provoked particularly lively debate in the wide audience drawn to such an event. The role of FI polymorphisms in disease will also make this work of more general interest to the public at large.

Complement Factor I (FI) plays a key role in regulating the complement in vertebrates by cleaving (in the presence of cofactors) C3b and C4b to inactivate the convertases. FI ensures that self-cells survive despite the low level of complement activation and is also responsible for maintenance of normal C3 levels in serum. Despite these important biological roles no detailed structural information is available for any part of FI. This application aims to use X-ray crystallography to solve near-atomic structures to illuminate FI biology. Several forms of FI will be targeted including human, bovine and pig native and deglycosyalted forms in addition to expressed or proteolytically generated fragments. Such data will allow, for the first time, generation of an atomic framework to allow full understanding of the mass of biochemical and functional data already in the FI literacture.