: “The small, intricate life of a clathrin coat” 

In this talk I’ll start by showing you some snapshots of events in my career, including how I became interested the protein clathrin. Clathrin forms part of the machinery enabling cells to selectively absorb molecules they need to survive by forming a protein coat around transport vesicles made from the plasma membrane. The focus of my research centres on how the remarkable lattice structure clathrin makes around these vesicles is formed and the role this plays in endocytosis. I’ll present two projects where we have used cryo-electron microscopy to understand the structure and function of clathrin complexes. In the first we determined structures of clathrin cage lattices with five different types of geometry and obtained a higher resolution map that we used to build a molecular model for clathrin. Fitting this into the lower resolution cage structures provided insights into how cages are formed and what may lead to the wider variety of lattice structures we see in cells. In the second story I will show how one of the key binding partners of clathrin, AP2, interacts with these cages and discuss the significance of differences shown in recently published structures. I’ll also show how integrating the structural work with cell biology studies has revealed a key role for the beta2-appendage subunit within AP2 in driving forward clathrin polymerisation and coated vesicle formation. Beyond clathrin and AP2 there are many more proteins involved in clathrin-mediated endocytosis. We are currently investigating how the wider network of adaptor proteins engages with the central clathrin machinery and whether common principles can be applied to understanding the mechanics of this intriguing cellular process.