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We are working on the molecular mechanisms in assembly of clathrin-coated vesicles and related membrane trafficking systems. The principal technique we use is X-ray crystallography to determine the structures of components, often as domains, and their complexes. The structural work is closely linked to functional studies, much of it done with our close collaborators Harvey McMahon in the Neurobiology Division and David Owen in the Cambridge Institute for Medical Research. |
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Coated vesicles consist of an inner membrane layer with cargo proteins embedded in it, and an outer scaffold layer (clathrin), with the two layers linked by proteins which recognise two different components (other proteins or lipid headgroups). This intermediate layer contains adaptors which recognise cargo and link to clathrin and other components; and accessory proteins which form part of the elaborate network of interactions required for assembly, disassembly and regulation. |
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| We have determined crystal structures of a number of domains and components of the system. These include all folded parts of the heterotetrameric AP2 complex (the core, and the C-terminal domains of the alpha, beta and mu subunits, and the phosphoinositide binding domains of CALM (AP180), and epsin, the BAR domains of Amphiphysin and Endophilin, the FBAR domain of FCHO2, and the SNARE/adaptor complex of VAMP7/Hrb (see gallery of structures). For more information on studies of function, see the group web-pages of Harvey McMahon and David Owen |
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