Molecular warfare: A structural biology view on pathogen weapons — GbpA from Vibrio cholerae — and host defenses — Vg from the honey bee

Abstract

The fight between pathogens and their hosts is almost as old as life on earth. Proteins are among the most important weapons used by pathogens and their hosts in the molecular warfare that underlies pathogenesis. This thesis has explored two protein targets involved in pathogenesis; one from a pathogen, namely N‑acetylglucosamine binding protein A (GbpA) from Vibrio cholerae, and one from a host, vitellogenin (Vg) from the honey bee. GbpA is used by the bacteria to colonize the human intestine. In addition, the protein helps the bacteria to survive in the water by colonizing plankton. This happens when GbpA binds to chitin, which it can also degrade. Our studies on GbpA have shed light on how the protein is stabilised and how it binds to chitin. In addition, we have gained insight into the mechanisms by which chitin is degraded, which can be exploited for making biofuels. Vg is fundamental for honey bee health. It is important for immunity and plays a central role in bee metabolism, social behaviour and longevity. Honey bees are ecologically and economically important as pollinators. Our structural biology work on Vg represents a very significant step forward in understanding the protein at the atomic level.