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Erik Zuiderweg

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Primary Appointment: Biological Chemistry Dept
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  NMR methodology has now matured to the point that the systems upto 100 kDa can be studied at atomic level resolution. The proteins are in solution and carry out the conformational changes and dynamic interactions necessary for function while the heteronuclear multi-dimensional NMR experiments are running.

Our group applies all aspects of these methodologies to study Hsp70 protein-folding chaperone proteins in solution. Hsp70s mediate trafficking, triaging, folding, unfolding and refolding of other proteins in vivo, from bacteria to man. The group’s high-resolution solution structure determinations of Hsp70 domains, as well as studies of atom-resolved dynamics and ligand interactions, have led to the formulation of an allosteric mechanism for these proteins. These mechanisms are being investigated in depth with large constructs (up to 60 kDa) that have become accessible for TROSY NMR studies by using 800 MHz equipment. We discover that these active allosteric constructs in solution change their conformation in upon ligand binding. We are also investigating complexes of chaperone and co-chaperone proteins in different allosteric states

Dynamics (local motion) is an essential component of biological functioning. Without motion, proteins cannot accommodate ligands, carry out chemistry, be allosterically active or be thermally stable. Our credo is: “Where it matters, it moves!”.
The group is working on the fundamental problem of the modeling of local motions. In several small proteins, the group has found evidence for correlated motions, for conformational change dynamics in enzyme active sites and for large changes in entropy contained in the dynamics of the protein backbone upon ligand binding.