Phil Evans

Structural studies of endocytosis components
pre@mrc-lmb.cam.ac.uk

Phil Evans began his research career as a student solving the crystal structure of phosphoglycerate kinase at Oxford University at a time when the X-ray crystallography of proteins was much slower than it is now. Following his Chemistry degree, D.Phil and a short post-doc in Oxford, he moved to the LMB in 1976 to work on a classic allosteric enzyme, phosphofructokinase, and with a series of crystal structures and biochemical studies over a period of 15 years defined the structural mechanism of its cooperativity and allosteric regulation. Following a collaboration with Kiyoshi Nagai in his early work on protein-RNA complexes, he worked on methylmalonyl-CoA mutase (with Peter Leadlay), solving the first structure of an enzyme that uses coenzyme B12, adenosylcobalamin. Since the late 1990s he has worked on the structure and function of proteins involved in vesicle trafficking and endocytosis, with Harvey McMahon and David Owen.

As a crystallographer, he has always found it valuable to collaborate with other groups with complementary expertise in biochemistry and cell biology, since the structure alone is not sufficient to understand function. He also continues his long-term interest in software developments in the techniques of X-ray crystallography, mainly in the initial processing of diffraction data, and has been involved in the UK-wide (and international) crystallographic software collaboration CCP4 since its inception in 1979.

He was elected a member of the European Molecular Biology Organisation in 2001 and a Fellow of the Royal Society in 2005.


Macromolecules are moved into cells and between cellular compartments by the movement of membrane vesicles containing protein and lipid cargo. The formation of these vesicles involves the assembly of complex protein machinery to invaginate the membrane, typically forming a polyhedral coat of clathrin around the vesicle.

We have been studying the structure and function of protein components of the clathrin-mediated endocytosis and other related systems, using X-ray crystallography, in collaboration with Harvey McMahon and with David Owen (Department of Clinical Biochemistry, Cambridge). This has led to a complete structure of one of the major players, the heterotetrameric AP2 adaptor complex, as well as parts of other components.

As well as protein-protein interactions, the endocytic system involves interactions between soluble proteins and the membrane. A number of endocytic proteins bend membranes into the tight curvature required for the formation of vesicles, and we have been investigating how this is done: for example, BAR domains have an intrinsic curved shape and also insert amphipathic helices into the membrane.

On the basis of the structures, mutants can be designed and used to probe function both in vitro and in vivo. The aim is to build up a complete structural and functional model of vesicle formation and its regulation, and to understand the difference in the trafficking pathways which run between different cell compartments.

Published research