Bernard T. Kelly, Airlie J. McCoy, Kira Späte, Sharon E. Miller, Philip R. Evans, Stefan Höning and David J. Owen (2008)
A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex
Nature, 456, 976-979
Lauren P. Jackson, Bernard T. Kelly, Airlie J. McCoy, Thomas Gaffry, Leo C. James, Brett M. Collins, Stefan Höning, Philip R. Evans, and David J. Owen (2010)
A Large-Scale Conformational Change Couples Membrane Recruitment to Cargo Binding in the AP2 Clathrin Adaptor Complex.
Cell 141, 1220–1229.
Philip R. Evans (2011)
An introduction to data reduction: space-group determination, scaling and intensity statistics.
Acta Cryst. D67, 282-292
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Group Members
- Richard Suckling
- Inmaculada Pérez Dorado
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| 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.
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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.
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Group Leaders 
