RESEARCH PROFILE

The research in my laboratory involves investigating the structure and mechanism of clathrin coated vesicle formation during clathrin-mediated endocytosis using a range of structural and biophysical techniques.

Receptor-mediated endocytosis allows a cell to choose and absorb the substances it requires. During endocytosis a clathrin-coated vesicle is formed which contains only specifically selected cargo. The clathrin coat is central to the ability of the vesicle to choose its contents and we aim, through a combination of structural and biophysical analysis to determine the factors that control its formation and disassembly

We are currently investigating how the molecular chaperone, Hsc70, and its cofactor auxilin, cause clathrin cage disassembly in vitro. We are using two approaches to investigate this. In the first we use 3D cryo-electron microscopy techniques to analyse the structure of purified clathrin cages bound to a range of proteins including Hsc70 and auxilin. In the second approach we monitor the kinetics of the process of clathrin cage disassembly using a range of biophysical techniques such as fluorescence anisotropy, stopped flow kinetics, isothermal titrating calorimetry and light scattering. We are now broadening our studies to investigate the part played by adaptor proteins and nucleotide exchange factors in the formation and disassembly of clathrin cage complexes.

Dr Smith is the Director of the Biological Electron Microscopy Facility at Warwick
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RESEARCH PROJECTS

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SELECTED PUBLICATIONS

• Dr Corinne J Smith,Rothnie A, Clarke AR, Kuzmic P, Cameron A, (2011) 'A sequential mechanism for clathrin cage disassembly by 70-kDa heat-shock cognate protein (Hsc70) and auxilin. ' Proceedings Of The National Academy Of Sciences (USA) 108 (17), 6927 - 6932 (0027-8424)
• Baglieri, J., Beck, D., Vasisht, N., Smith, Corinne J. and Robinson, Colin(2011) 'Structure of the TatA paralog, TatE, suggests a structurally homogeneous from of Tat protein translocase that transports folded proteins of differing diameter.' Journal Of Biological Chemistry 287 (10), 7335 - 7344 (0021-9258)
• Soufi, A., Sawasdichai, A., Shukla, A. Noy, P., Dafforn, T.R. Smith, C., Jayaraman, P-S. and Gaston, K.(2010) 'DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers' Nucleic Acids Research 38 (21), 7513 - 7525 (0305-1048) [article]
• Knowles, T. J., Finka, R., Smith, C., Lin, Y. -P., Dafforn, T. and Overduin, M.(2009) 'Membrane proteins solubilized intact in lipid containing nanoparticles bounded by styrene maleic acid copolymer' Journal Of American Chemical Society 131 (22), 7484 - 7485 (0002-7863)
• Edeling ME, Smith CJ , Owen DJ (2006) 'Life of a clathrin coat: insights from clathrin and AP structures', Nature Reviews: Molecular Cell Biology, 32 - 44, [Review]

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