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Professor Jane Clarke

Abstract:

Protein folding, misfolding and assembly.    In my laboratory we use a multidisciplinary approach to ask fundamental questions about protein folding, misfolding and assembly. We combine biophysical methods (both ensemble and single molecule) with structural biology, protein engineering, bioinformatics and simulations, and have a number of active collaborations with groups elsewhere in the UK, in Europe and in the USA.    Current areas of interest in the laboratory include:    Folding upon binding of intrinsically disordered proteins: IDPs are central in many vital cellular processes, including development, apoptosis and signalling.  We are investigating many of the biophysical aspects of the folding-upon-binding of IDPs – binding mechanism, specificity, the importance of disorder, allostery, and competition for ligands.  This is a relatively new field and so there are many important unanswered questions to explore.    Folding (and misfolding) multidomain proteins.  Most proteins in the human proteome comprise more than one independently folded domain. How is the folding of one domain affected by its neighbours (in terms of stability, folding kinetics and mechanism?) Importantly, since the local concentration of domains is high, how do multidomain proteins avoid misfolding? We have detected misfolding in all-beta proteins – are the same challenge faced by alpha helical proteins? We are investigating all these questions using a number of differnt multidomain proteins, with a combination of ensemble biophysics, time resolved single molecule FRET techniques, bioinformatics and simulation.      If any student is interested a project in the general area of protein folding misfolding and assembly, they should come to visit the lab, to discuss specific ideas.

References:

  1. Rogers, J.M. Steward, A. & Clarke, J. (2013) Folding and binding of an intrinsically disordered protein: fast, but not ‘diffusion-limited’. J. Am. Chem. Soc., 135, 1415−1422  
  2. Borgia, M.B., Borgia, A., Best, R.B., Steward, A., Nettels, D., Wunderlich, B., Schuler, B. & Clarke, J. (2011) Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins. Nature 474, 662-665

Professor Jane Clarke

Professor Jane Clarke
Department of Chemistry
Office Phone: 01223 336426